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molecular epidemiology of a/h3n2 and a/h1n1 influenza virus during a single epidemic season in the united states.to determine the spatial and temporal dynamics of influenza a virus during a single epidemic, we examined whole-genome sequences of 284 a/h1n1 and 69 a/h3n2 viruses collected across the continental united states during the 2006-2007 influenza season, representing the largest study of its kind undertaken to date. a phylogenetic analysis revealed that multiple clades of both a/h1n1 and a/h3n2 entered and co-circulated in the united states during this season, even in localities that are distant fro ...200818725925
[epidemic strains influenza viruses a and b in the 2005-2006 season in russia].investigations indicated that the epidemic upsurge of influenza morbidity in the 2005-2006 season in russia was caused by the active circulation of influenza viruses a and b. the center for ecology and epidemiology of influenza, d. i. ivanovsky institute of virology, russian academy of medical sciences, studied 182 epidemic strains. a hundred and thirteen influenza viruses a(h3n2) were similar to the reference a/california/07/2004 or were its antigenic variants. thirteen influenza virus a(h1n1) ...200818756810
epidemiological and virological assessment of influenza activity in europe, during the 2006-2007 winter.influenza surveillance in europe is based on influenza surveillance networks that cooperate and share information through the european influenza surveillance scheme (eiss). eiss collected clinical and virological data on influenza in 33 countries during the 2006-2007 winter. influenza activity started around 1 january and first occurred in greece, scotland and spain. it then moved gradually across europe from south to north and lasted until the end of march. in 29 out of 33 countries, the consul ...200818761888
[molecular analyses of human influenza viruses. circulation of new variants since 1995/96].the evolution of influenza viruses is increasingly pursued by molecular analyses that complement classical methods. the analyses focus on the two surface proteins hemagglutinin (ha) and neuraminidase (na) which determine the viral antigenic profile. influenza a(h3n2) viruses are exceptionally variable, so that usually at least two virus variants cocirculate at the same time. together with influenza b viruses they caused approximately 90% of influenza virus infections in germany during the last 1 ...200818773168
seroprevalence and genetic evolutions of swine influenza viruses under vaccination pressure in korean swine herds.an overall 8,427 total of blood samples collected from growing to finishing pigs were submitted for diagnosis of swine influenza virus infection between january 2002 and december 2006. sera from 2002 to 2005 were examined for antibodies against four different swine influenza subtypes using the hemagglutination inhibition test to investigate seroprevalence rates by natural infection in korean swine herds while nasal swabs and lung tissue samples were used for viral isolation. the natural infectio ...200818789984
prevalence of avian influenza viruses, borrelia garinii, mycobacterium avium, and mycobacterium avium subsp. paratuberculosis in waterfowl and terrestrial birds in slovakia, 2006.the prevalence of borrelia, mycobacteria and avian influenza virus (aiv) infections, together with the distribution of different aiv subtypes, was studied in migratory waterfowl and terrestrial birds trapped in three localities in slovakia during 2006. samples obtained from waterfowl captured in the senianske ponds area of eastern slovakia showed the highest diversity of aiv isolates. a total of 13 different subtypes were detected in 19 samples from this location (h1n2, h2n2, h3n2, h6n6, h7n6, h ...200818798030
role of viral hemagglutinin glycosylation in anti-influenza activities of recombinant surfactant protein d.surfactant protein d (sp-d) plays an important role in innate defense against influenza a viruses (iavs) and other pathogens.200818811961
high-throughput screening of a 100,000-compound library for inhibitors of influenza a virus (h3n2).using a highly reproducible and robust cell-based high-throughput screening (hts) assay, the authors screened a 100,000-compound library at 14- and 114-microm compound concentration against influenza strain a/udorn/72 (h3n2). the "hit" rates (>50% inhibition of the viral cytopathic effect) from the 14- and 114-microm screens were 0.022% and 0.38%, respectively. the hits were evaluated for their antiviral activity, cell toxicity, and selectivity in dose-response experiments. the screen at the low ...200818812571
compatibility among polymerase subunit proteins is a restricting factor in reassortment between equine h7n7 and human h3n2 influenza viruses.reassortment is an important driving force for influenza virus evolution, and a better understanding of the factors that affect this process could improve our ability to respond to future influenza pandemics and epidemics. to identify factors that restrict the generation of reassortant viruses, we cotransfected human embryonic kidney cells with plasmids for the synthesis of viral rnas of both a/equine/prague/1/56 (prague; h7n7) and a/yokohama/2017/03 (yokohama; h3n2) viruses together with the su ...200818815312
universal influenza vaccination and live attenuated influenza vaccination of children.influenza is an uncontrolled epidemic disease that is vaccine preventable. each winter the peak of medically attended acute respiratory illness coincides with the peak of influenza virus activity. the anatomy of an urban influenza epidemic is presented highlighting the role of children in the spread of influenza. the efficacy and safety of the live attenuated influenza vaccine (laiv) for children are documented and the indirect effectiveness (herd protection) of vaccinating schoolchildren is dem ...200818820568
experimental evolution of human influenza virus h3 hemagglutinin in the mouse lung identifies adaptive regions in ha1 and ha2.the genetic basis for virulence and host switching in influenza a viruses (fluav) is largely unknown. because the hemagglutinin (ha) protein is a determinant of these properties, ha evolution was mapped in an experimental model of mouse lung adaptation. variants of prototype a/hong kong/1/68 (h3n2) (wild-type [wt] hk) human virus were selected in both longitudinal and parallel studies of lung adaptation. mapping of ha mutations found in 11 independently derived mouse-adapted populations of wt hk ...200818829764
emergence of amantadine-resistant h3n2 avian influenza a virus in south korea.we found a relatively high frequency of unique amantadine-resistant h3n2 and h9n2 avian influenza viruses (val27ile on m2 protein) isolated from live poultry markets in south korea and confirmed that a val27ile single substitution in the m2 protein is enough to acquire the amantadine resistance phenotype by using reverse-genetically created human-avian reassortant viruses.200818845822
positive selection operates continuously on hemagglutinin during evolution of h3n2 human influenza a virus.it has been proposed that antigenic evolution of hemagglutinin 1 (ha1) for h3n2 human influenza a virus was punctuated. in the population genetic analysis, however, it was controversial whether positive selection operated on ha1 in a punctuated manner for the branches of the phylogenetic tree where transitions to new antigenic clusters occurred (c branches), or continuously. in the molecular evolutionary analysis, positive selection was detected for the trunk (t) branches but the relationship be ...200818848975
impact of influenza a virus neuraminidase mutations on the stability, activity, and sensibility of the neuraminidase to neuraminidase inhibitors.the influenza neuraminidase plays a critical role in the spread of the influenza a and b viruses. through the cleavage of terminal sialic acid from glycoconjugates, it facilitates the elution of progeny virions from infected cells and prevents their self-aggregation.200818065262
dual infections by influenza a/h3n2 and b viruses and by influenza a/h3n2 and a/h1n1 viruses during winter 2007, corsica island, france.the investigation of dual influenza infection human cases is of major interest specifically for the control of new emerging influenza strains.200818069055
a multiplex real-time rt-pcr for detection and identification of influenza virus types a and b and subtypes h5 and n1.a multiplex real-time rt-pcr method for the simultaneous detection of influenza virus types a and b and identification of subtypes h5 and n1 in a single tube is described. the method was developed with four sets of primers and probes which were specific to influenza virus (sub)types a, b, h5, and n1, and evaluated by using a total of 40 influenza virus reference strains, including 17 avian influenza a (12 h5n1, 1 h1n1, 1 h3n2, 1 h4n6, 1 h7n3, and 1 h9n2), 18 human influenza a (11 h3n2, 6 h1n1 an ...200818078675
novel reassortant of swine influenza h1n2 virus in germany.european porcine h1n2 influenza viruses arose after multiple reassortment steps involving a porcine influenza virus with avian-influenza-like internal segments and human h1n1 and h3n2 viruses in 1994. in germany, h1n2 swine influenza viruses first appeared in 2000. two german h1n2 swine influenza virus strains isolated from pigs with clinical symptoms of influenza are described. they were characterized by the neutralization test, haemagglutination inhibition (hi) test and complete sequencing of ...200818089751
genetic and antigenic analysis of epidemic influenza viruses isolated during 2006-2007 season in taiwan.influenza viruses are some of the most active pathogens in taiwan. the monitoring influenza activity has been coordinated by the centers for diseases control, taiwan, and the surveillance is based on integrated clinical and virological surveillance components. data from sentinel physician networks and other sources, mainly hospitals were collected. during 2006-07 season, a total of 1724 cases of laboratory-confirmed influenza were reported by collaborating laboratories and sentinels, which was f ...200818098164
protective and cross-protective mucosal immunization of mice by influenza virus type a with bacterial adjuvant.mucosal immunization by inactivated viruses often fails to evoke a sufficient immune response. intensive efforts have been made to enhance the response by suitable adjuvants. we used the g+ nonpathogenic delipidated bacterium bacillus firmus with pronounced immunostimulatory properties as an adjuvant for immunizing mice with inactivated influenza virus type a. balb/c mice were immunized intratracheally with inactivated influenza a h1n1 and h3n2 viruses. the production of antibodies in sera and s ...200818160106
molecular characterization and phylogenetic analysis of h1n1 and h3n2 human influenza a viruses among infants and children in thailand.the annual influenza outbreaks can cause a high mortality rate among infants and children. in the tropics, influenza shows no clear dependence on seasons. in the present study, we performed molecular and phylogenetic analysis of h1n1 and h3n2 influenza virus isolated from infants and children diagnosed with respiratory tract illness between february 2006 and february 2007. a total of 33 samples (10.92%) were found positive for human influenza virus infection. characterization of the hemagglutini ...200818160168
rapid differentiation of influenza a virus subtypes and genetic screening for virus variants by high-resolution melting analysis.we assessed the use of high-resolution melting (hrm) analysis for the rapid identification of influenza a virus subtypes and the detection of newly emerging virus variants. the viral matrix gene was amplified by lightcycler real-time reverse transcription-pcr (rt-pcr) in the presence of the lcgreen i fluorescent dye. upon optimization of the assay conditions, all the major influenza a virus subtypes, including h1n1, h3n2, h5n1, h7n3, and h9n2, were amplifiable by this method and had a pcr produc ...200818174299
glycan topology determines human adaptation of avian h5n1 virus hemagglutinin.a switch in specificity of avian influenza a viruses' hemagglutinin (ha) from avian-like (alpha2-3 sialylated glycans) to human-like (alpha2-6 sialylated glycans) receptors is believed to be associated with their adaptation to infect humans. we show that a characteristic structural topology--and not the alpha2-6 linkage itself--enables specific binding of ha to alpha2-6 sialylated glycans and that recognition of this topology may be critical for adaptation of ha to bind glycans in the upper resp ...200818176555
bioinformatics models for predicting antigenic variants of influenza a/h3n2 virus.motivation: continual and accumulated mutations in hemagglutinin (ha) protein of influenza a virus generate novel antigenic strains that cause annual epidemics. results: we propose a model by incorporating scoring and regression methods to predict antigenic variants. based on collected sequences of influenza a/h3n2 viruses isolated between 1971 and 2002, our model can be used to accurately predict the antigenic variants in 1999-2004 (agreement rate = 91.67%). twenty amino acid positions identifi ...200818187440
genetic evolution of swine influenza a (h3n2) viruses in china from 1970 to 2006.pigs are susceptible to both human and avian influenza viruses and have been proposed to be intermediate hosts, or mixing vessels, for the generation of pandemic influenza viruses through reassortment or adaptation to the mammalian host. in this study, we summarize and report for the first time the coexistence of wholly human-like h3n2 viruses, double-reassortant h3n2 viruses, and triple-reassortant h3n2 viruses in pigs in china by analyzing the eight genes of swine influenza a (h3n2) viruses fo ...200818199784
genetic and antigenic relatedness of h3 subtype influenza a viruses isolated from avian and mammalian species.in 2004, we isolated triple reassortant h3n2 influenza viruses from turkey breeder hens in ohio and illinois. the illinois flock was vaccinated twice with an inactivated h3n2 vaccine containing a swine origin virus before the outbreak. additionally, a commercial inactivated vaccine containing an h3n4 virus of duck origin is being used in some turkey breeders. this prompted us to initiate a comparative study on the antigenic and genetic relatedness of various h3 subtype influenza viruses isolated ...200818206275
healthy human subjects have cd4+ t cells directed against h5n1 influenza virus.it is commonly perceived that the human immune system is naive to the newly emerged h5n1 virus. in contrast, most adults have been exposed to influenza a h1n1 and h3n2 viruses through vaccination or infection. adults born before 1968 have likely been exposed to h2n2 viruses. we hypothesized that cd4(+) t cells generated in response to h1n1, h3n2, and h2n2 influenza a viruses also recognize h5n1 epitopes. tetramer-guided epitope mapping and ag-specific class ii tetramers were used to identify h5n ...200818209073
prevalence of and risk factors for influenza in southern ontario swine herds in 2001 and 2003.this research included 2 prevalence studies and a risk-factor investigation conducted in 2001 at 93 sites with sows only, finishers only, or both. in 2001, 1300 serum samples from sows in 65 herds and 720 serum samples from finisher pigs in 72 herds were tested for antibodies to swine influenzavirus (siv) of h1n1 subtype with an enzyme-linked immunosorbent assay (elisa). in 2003, 1140 serum samples from sows in 76 herds were tested for antibodies to siv of h3n2 subtype with a hemagglutination-in ...200818214156
sublingual vaccination with influenza virus protects mice against lethal viral infection.we assessed whether the sublingual (s.l.) route would be an effective means of delivering vaccines against influenza virus in mice by using either formalin-inactivated or live influenza a/pr/8 virus (h1n1). sublingual administration of inactivated influenza virus given on two occasions induced both systemic and mucosal antibody responses and conferred protection against a lethal intranasal (i.n.) challenge with influenza virus. coadministration of a mucosal adjuvant (mcta-ltb) enhanced these res ...200818227512
flublok, a recombinant influenza vaccine.protein sciences corp and umn pharma inc are developing flublok, an injectable trivalent influenza vaccine formulation composed of recombinant influenza hemagglutinin (ha) proteins that match the ha from the three influenza isolates that currently circulate in humans (h1n1, h3n2 and b), for the potential prevention of influenza virus infection. phase iii clinical trials to compare flublok and a licensed trivalent influenza vaccine for immunogenicity, safety and efficacy in preventing naturally o ...200818228185
time lines of infection and disease in human influenza: a review of volunteer challenge studies.the dynamics of viral shedding and symptoms following influenza virus infection are key factors when considering epidemic control measures. the authors reviewed published studies describing the course of influenza virus infection in placebo-treated and untreated volunteers challenged with wild-type influenza virus. a total of 56 different studies with 1,280 healthy participants were considered. viral shedding increased sharply between 0.5 and 1 day after challenge and consistently peaked on day ...200818230677
influenza detection and subtyping by reverse transcriptase polymerase chain reaction-restriction fragment length polymorphism for laboratory surveillance in brazil.a duplex reverse transcriptase polymerase chain reaction-restriction fragment length polymorphism for influenza virus subtyping was applied to 412 patient samples. the assay was able to discriminate all 47 influenza a h1n1 and h3n2 viruses. this rapid technique assessed if positive samples were current circulating strains or an emergent one and could be used as the 1st test in prepandemic stages.200818234464
current and future antiviral therapy of severe seasonal and avian influenza.the currently circulating h3n2 and h1n1 subtypes of influenza a virus cause a transient, febrile upper respiratory illness in most adults and children ("seasonal influenza"), but infants, the elderly, immunodeficient and chronically ill persons may develop life-threatening primary viral pneumonia or complications such as bacterial pneumonia. by contrast, avian influenza viruses such as the h5n1 virus that recently emerged in southeast asia can cause severe disease when transferred from domestic ...200818328578
identification of amino acids in the ha of h3 influenza viruses that determine infectivity levels in primary swine respiratory epithelial cells.in the late 1990s, triple reassortant h3n2 influenza a viruses emerged and spread widely within the swine population of the united states. we have shown previously that an isolate representative of this lineage of viruses, a/swine/minnesota/593/99 (sw/mn), has higher infectivity and accelerated replication kinetics in pigs, compared to a human-lineage h3n2 virus isolated from a pig during the same time period, a/swine/ontario/00130/97 (sw/ont [landolt, g.a., karasin, a.i., phillips, l., olsen, c ...200818329747
in vitro and in vivo investigations on the antiviral activity of a series of mixed-valence rare earth borotungstate heteropoly blues.a series of mixed-valence rare earth borotungsto-heteropoly blues, k15h2[ln(bw9w2o39)2].28h2o (ln2, ln=la, ce, pr, nd, sm, eu, gd), have been prepared and characterized by ir, uv, xps, esr and electrochemistry. the cytotoxicity and antiviral activity of these rare earth borotungstate heteropoly blues were investigated against influenza a(fluva) strain (a/h1n1/jingfang/1/91 and a/h3n2/jingfang/30/95) and influenza virus b(fluvb) (b/hufang/1/87) in mdck cells. the results show that k15h2[pr(bw9w2o ...200818342405
ecology of h3 avian influenza viruses in korea and assessment of their pathogenic potentials.to determine the genetic origins of novel h3 avian influenza viruses of chickens and ducks in korea, genetic characterization of h3 avian influenza viruses isolated from live poultry markets and migratory aquatic birds in south korea during 2004-2006 was conducted. phylogenetic analysis revealed that at least four novel genotypes of h3n2 and two genotypes of h3n6 avian influenza viruses were co-circulating in backyard poultry of korea. the viruses were reassortants between h9n2 viruses of korean ...200818343836
antibodies induced by the ha2 glycopolypeptide of influenza virus haemagglutinin improve recovery from influenza a virus infection.the haemagglutinin (ha) of influenza a virus consists of two glycopolypeptides designated ha1 and ha2. antibodies recognizing ha1 inhibit virus haemagglutination, neutralize virus infectivity and provide good protection against infection, but do not cross-react with the ha of other subtypes. little is known regarding the biological activities of antibodies against ha2. to study the role of antibodies directed against ha2 during influenza virus infection, two vaccinia virus recombinants (rvvs) we ...200818343837
origin of the 1918 spanish influenza virus: a comparative genomic analysis.to test the avian-origin hypothesis of the 1918 spanish influenza virus we surveyed influenza sequences from a broad taxonomic distribution and collected 65 full-length genomes representing avian, human and "classic" swine h1n1 lineages in addition to numerous other swine (h1n2, h3n1, and h3n2), human (h2n2, h3n2, and h5n1), and avian (h1n1, h4n6, h5n1, h6n1, h6n6, h6n8, h7n3, h8n4, h9n2, and h13n2) subtypes. amino acids from all eight segments were concatenated, aligned, and used for phylogenet ...200818353690
homologous recombination is very rare or absent in human influenza a virus.to determine the extent of homologous recombination in human influenza a virus, we assembled a data set of 13,852 sequences representing all eight segments and both major circulating subtypes, h3n2 and h1n1. using an exhaustive search and a nonparametric test for mosaic structure, we identified 315 sequences (approximately 2%) in five different rna segments that, after a multiple-comparison correction, had statistically significant mosaic signals compatible with homologous recombination. of thes ...200818353939
cross-recognition of avian h5n1 influenza virus by human cytotoxic t-lymphocyte populations directed to human influenza a virus.since the number of human cases of infection with avian h5n1 influenza viruses is ever increasing, a pandemic outbreak caused by these viruses is feared. therefore, in addition to virus-specific antibodies, there is considerable interest in immune correlates of protection against these viruses, which could be a target for the development of more universal vaccines. after infection with seasonal influenza a viruses of the h3n2 and h1n1 subtypes, individuals develop virus-specific cytotoxic t-lymp ...200818353950
antibody contributes to heterosubtypic protection against influenza a-induced tachypnea in cotton rats.influenza virus infection or vaccination evokes an antibody response to viral hemagglutinin (ha) and neuraminidase (na) surface glycoproteins, which results in immunity against influenza a viruses of the same ha and na subtype. a heterosubtypic immune response that offers some protection against different influenza a subtypes has been suggested from epidemiologic studies in human influenza outbreaks, and has been induced in experimental animal models. original studies of such cross-protection sh ...200818355405
molecular evolution of influenza a (h3n2) viruses circulated in fujian province, china during the 1996-2004 period.we studied the genetic and epidemic characteristics of influenza a (h3n2) viruses circulated in human in fujian province, south of china from 1996 to 2004. phylogenetic analysis was carried out for genes encoding hemagglutinin1 (ha1) of influenza a virus (14 new and 11 previously reported reference sequences). our studies revealed that in the 8 flu seasons, the mutations of ha1 genes occurred from time to time, which were responsible for about four times of antigenic drift of influenza h3n2 viru ...200818368315
[comparative analysis of the susceptibility and productivity of respiratory tract target cells of mice and rats exposed to inflienza virus in vitro].the levels of susceptibility to influenza virus a/aichi/2/68 h3n2 and the virus yield were determined using primary cells of the trachea and lungs of cd-1 mice and wistar rats, and for 3 sets of cells obtained from primary lung cells of the both species by centrifugation in the gradient of density and by sedimentation on a surface. the values of id50 virus dose for 10(6) cells and virus yield per 1 infected cell determined for primary mice cells were 4.0+/-0.47 and 3.2+/-0.27 igeid50 (lung cells ...200818368764
protective efficacy of an aerosol preparation, obtained from geranium sanguineum l., in experimental influenza infection.a polyphenol-rich extract from the aerial roots of the medicinal plant geranium sanguineum l. (pc) protected mice from mortality in the experimental influenza a/aichi/2/68 (h3n2) virus infection. to provide evidence how a maximum therapeutic benefit can be derived of this preparation, it was inoculated by 6 different routes. it was found that the aerosol application of pc was highly effective. in the dose 5.4 mg/ml, applied according to a prophylactic-therapeutic schedule, the extract exhibited ...200818380405
identification of a human monoclonal fab with neutralizing activity against h3n2 influenza a strain from a newly constructed human fab library.a combinatorial fab library was constructed in pcomb3h phagemid vectors, using rna from peripheral blood lymphocytes of a healthy volunteer who had recovered from an influenza a virus infection. the library contained approximately 1.3 x 10(8)e. coli transformants. bio-panning was carried out against an influenza vaccine containing components of influenza a/new caledonia/20/99 (h1n1), a/panama/2007/99 (h3n2), and b/shandong/7/97 for the enrichment of phages displaying human fab specific to the vi ...200818402598
the genomic and epidemiological dynamics of human influenza a virus.the evolutionary interaction between influenza a virus and the human immune system, manifest as 'antigenic drift' of the viral haemagglutinin, is one of the best described patterns in molecular evolution. however, little is known about the genome-scale evolutionary dynamics of this pathogen. similarly, how genomic processes relate to global influenza epidemiology, in which the a/h3n2 and a/h1n1 subtypes co-circulate, is poorly understood. here through an analysis of 1,302 complete viral genomes ...200818418375
development of a high-throughput alamar blue assay for the determination of influenza virus infectious dose, serum antivirus neutralization titer and virus ca/ts phenotype.flumist is an intranasal influenza live vaccine containing two influenza a strains (currently h1n1 and h3n2) and one b strain (yamagata or victoria lineage). characterization of the vaccine requires determination of the median tissue culture infectious dose (tcid(50)) titer, serum antivirus neutralization titer and vaccine cold adapted/temperature sensitive (ca/ts) phenotype. visual cytopathic effect (cpe) readings are used widely in viral assays, but these are subjective and labor intensive. in ...200818423899
effects of single-point amino acid substitutions on the structure and function neuraminidase proteins in influenza a virus.in order to clarify the effect of amino acid substitutions on the structure and function of the neuraminidase (na) protein of influenza a virus, we introduced single-point amino acid substitutions into the na protein of the a/tokyo/3/67 (h2n2) strain using pcr-based random mutation. the rate of tolerant random one amino acid substitutions in the na protein was 47%. rates of tolerant substitutions for the stalk and for the surface and inner portion of the head region of the na protein were 79, 54 ...200818426396
human influenza virus infection and apoptosis induction in human vascular endothelial cells.acute encephalopathy accompanying influenza virus infection results in brain and systemic organ failure mainly through vasogenic edema with high levels of inflammatory cytokines, such as blood tumor necrosis factor (tnf)-alpha and interleukin (il)-6, as well as the cytochrome c apoptosis marker. a highly virulent strain of avian influenza virus causes fatal infection in chickens by infecting vascular endothelial cells in systemic organs, inducing apoptosis therein. to verify the possibility of a ...200818428129
the course of fever following influenza virus infection in children treated with oseltamivir.although the effectiveness of oseltamivir against influenza virus infection is well known, there has been no report analyzing the detailed time course of fever following the drug treatment in children. oseltamivir was prescribed for 4 days to every child with a positive result for rapid immunological test for influenza virus during 2002--2003, 2003--2004, and 2004--2005 epidemics. only those who were 1-12 years of age and prescribed oseltamivir within 24 hr after the onset of fever were included ...200818428131
influenza exposure in united states feral swine populations.swine play an important role in the disease ecology of influenza. having cellular receptors in common with birds and humans, swine provide opportunities for mixed infections and potential for genetic reassortment between avian, human, and porcine influenza. feral swine populations are rapidly expanding in both numbers and range and are increasingly coming into contact with waterfowl, humans, and agricultural operations. in this study, over 875 feral swine were sampled from six states across the ...200818436668
transmission of avian influenza virus (h3n2) to dogs.in south korea, where avian influenza virus subtypes h3n2, h5n1, h6n1, and h9n2 circulate or have been detected, 3 genetically similar canine influenza virus (h3n2) strains of avian origin (a/canine/korea/01/2007, a/canine/korea/02/2007, and a/canine/korea/03/2007) were isolated from dogs exhibiting severe respiratory disease. to determine whether the novel canine influenza virus of avian origin was transmitted among dogs, we experimentally infected beagles with this influenza virus (h3n2) isola ...200818439355
plant-expressed ha as a seasonal influenza vaccine candidate.influenza is a globally important respiratory pathogen that causes a high degree of morbidity and mortality annually. although current vaccines are effective against virus infection, new strategies need to be developed to satisfy the global demand for an influenza vaccine. to address this point, we have engineered and produced the full-length hemagglutinin (ha) protein from the a/wyoming/03/03 (h3n2) strain of influenza in plants. the antigenicity of this plant-produced ha was confirmed by elisa ...200818440103
epidemiological survey of swine influenza a virus in selected wild boar populations in germany.the aim of this study was to evaluate the epidemiological situation of swine influenza virus (siv) infections in different wild boar populations in germany based on a serological surveillance in some bundeslaender (federal states) in connection with virological investigations in wild boar shot in northern germany (mecklenburg-western pomerania, district of nordvorpommern). altogether, 1245 sera from wild boar were tested using the hemagglutination inhibition test. the established seroprevalence ...200818440732
generation and evaluation of the trivalent inactivated reassortant vaccine using human, avian, and swine influenza a viruses.reassortant technology was used to obtain three interspecific reassortant influenza viruses using three influenza viruses of a/puerto rico/8/34(h1n1), a/swine/hebei/1/2005(h3n2) and a/chicken/guangdong/126/2002(h9n2). the high-growth reassortant strains were h9/pr8, h3/h9n2 and h1/h9n2 that contained hemagglutinin (ha) and neuraminidase (na) genes from the inactivated parental viruses and the other 6 internal genes from the live parental viruses. the trivalent formalin-inactivated vaccine, conta ...200818448208
genetic characterization of h1n1, h1n2 and h3n2 swine influenza virus in thailand.swine have been known to be a suitable host for influenza a virus. in thailand, phylogenetic analysis on swine influenza virus (siv) has as yet not been attempted. the present report presents molecular and phylogenetic analysis performed on siv in thailand. in this study, 12 siv isolates from the central and eastern part of thailand were subtyped and the molecular genetics of hemagglutinin and neuraminidase were elucidated. three subtypes, h1n1, h1n2 and h3n2, are described. phylogenetic analysi ...200818458812
a bivalent influenza vlp vaccine confers complete inhibition of virus replication in lungs.the conventional egg-grown influenza vaccines are trivalent. to test the feasibility of using multivalent influenza virus-like particles (vlps) as an alternative influenza vaccine, we developed cell-derived influenza vlps containing the hemagglutinin (ha) of the h1 subtype virus a/pr/8/34 or the h3 subtype virus a/aichi/2/68 (x31). mice immunized intramuscularly with bivalent influenza vlps containing h1 and h3 has induced neutralizing activities against the homologous and closely related h1n1 s ...200818468740
mdck-siat1 cells show improved isolation rates for recent human influenza viruses compared to conventional mdck cells.the ability to isolate and propagate influenza virus is an essential tool for the yearly surveillance of circulating virus strains and to ensure accurate clinical diagnosis for appropriate treatment. the suitability of mdck-siat1 cells, engineered to express increased levels of alpha-2,6-linked sialic acid receptors, as an alternative to conventional mdck cells for isolation of circulating influenza virus was assessed. a greater number of influenza a (h1n1 and h3n2) and b viruses from stored hum ...200818480230
one-step multiplex rt-pcr for detection and subtyping of swine influenza h1, h3, n1, n2 viruses in clinical samples using a dual priming oligonucleotide (dpo) system.the swine influenza virus (siv) h1n1, h1n2, and h3n2 subtypes circulate in korean farm. a novel multiplex rt-pcr (m-rt-pcr) was developed to detect and subtype swine influenza viruses. this m-rt-pcr assay could identify h1, h3, n1 and n2 from clinical samples in single tube reaction using dpo system. korean sivs are closely related to the united states influenza viruses, and primers were developed for siv from north american viruses and recently korean isolates. the sensitivity of the m-rt-pcr w ...200818486976
[molecular and genetic analysis of influenza a viruses isolated in russia, based on the neuraminidase and m2 protein gene sequence].the results of molecular analysis of 15 influenza a(h3n2) and 17-a(h1n1) epidemic strains isolated in the russian federation in 1995-2007 are described. the analysis on the m2 and neuraminidase influenza a virus genes was performed. the m2 sequences analysis among the remantadin resistant viruses demonstrated the s31n substitution in all strains. besides s31n substitution, additional mutations were detected in both proteins. mutations associated with s31n substitution were detected in each virus ...200818488446
influenza a virus abrogates ifn-gamma response in respiratory epithelial cells by disruption of the jak/stat pathway.the innate immunity to viral infections induces a potent antiviral response mediated by interferons (ifn). although ifn-gamma is detected during the acute stages of illness in the upper respiratory tract secretions and in the serum of influenza a virus-infected individuals, control of influenza a virus is not dependent upon ifn-gamma as evidenced by studies using anti-ifn-gamma ab and ifn-gamma(-/-) mice. thus, we hypothesized that ifn-gamma is not critical in host survival because influenza a v ...200818493979
genetic compatibility and virulence of reassortants derived from contemporary avian h5n1 and human h3n2 influenza a viruses.the segmented structure of the influenza virus genome plays a pivotal role in its adaptation to new hosts and the emergence of pandemics. despite concerns about the pandemic threat posed by highly pathogenic avian influenza h5n1 viruses, little is known about the biological properties of h5n1 viruses that may emerge following reassortment with contemporary human influenza viruses. in this study, we used reverse genetics to generate the 63 possible virus reassortants derived from h5n1 and h3n2 vi ...200818497857
a maximum likelihood method for detecting directional evolution in protein sequences and its application to influenza a virus.we develop a model-based phylogenetic maximum likelihood test for evidence of preferential substitution toward a given residue at individual positions of a protein alignment--directional evolution of protein sequences (deps). deps can identify both the target residue and sites evolving toward it, help detect selective sweeps and frequency-dependent selection--scenarios that confound most existing tests for selection, and achieve good power and accuracy on simulated data. we applied deps to align ...200818511426
an optimized electrofusion-based protocol for generating virus-specific human monoclonal antibodies.we sought to develop and optimize a hybridoma-based technology for generating human hybridomas that secrete virus-specific monoclonal antibodies for clinical diagnosis and therapy. we developed a novel electrofusion protocol for efficiently fusing epstein-barr virus (ebv)-transformed human b cells with myeloma partners. we tested seven myeloma cell lines and achieved highest efficiency when the hmma 2.5 line was used. we optimized the electrofusion process by improving cell treatments before and ...200818514220
prevention of symptomatic seasonal influenza in 2005-2006 by inactivated and live attenuated vaccines.the efficacy of influenza vaccines may vary annually. in 2004-2005, when antigenically drifted viruses were circulating, a randomized, placebo-controlled trial involving healthy adults showed that inactivated vaccine appeared to be efficacious, whereas live attenuated vaccine appeared to be less so.200818522501
heterologous ha dna vaccine prime--inactivated influenza vaccine boost is more effective than using dna or inactivated vaccine alone in eliciting antibody responses against h1 or h3 serotype influenza viruses.the trivalent inactivated vaccine (tiv) is used to prevent seasonal influenza virus infection in humans, however, the immunogenicity of this vaccine may be influenced by the priming effect of previous influenza vaccinations or exposure to antigenically related influenza viruses. the current study examines the immunogenicity of a clinically licensed tiv in rabbits naïve to influenza antigens. animals were immunized with either the licensed tiv, a bivalent (h1 and h3) ha dna vaccine or the combina ...200818538900
anti-influenza virus activities of flavonoids from the medicinal plant elsholtzia rugulosa.elsholtzia rugulosa (lamiaceae), a common chinese herb, is widely used in the treatment of cold and fever. in order to elucidate the action mechanism and the active principles from the plant against anti-influenza virus, the influenza virus neuraminidase (na) activity assay and in vitro antiviral activity assay were established, and the isolation of the active principles was guided by na activity. finally, 5 active constituents were obtained, namely apigenin ( 1), luteolin ( 2), apiin ( 3), galu ...200818553272
streptococcus suis type 2 culture supernatant enhances the infection ability of the swine influenza virus h3 subtype in mdck cells.swine influenza virus and streptococcus suis type 2 often occur as a clinical coinfection in pigs, the syndrome of which is more serious than the virus or bacterium sole infection. streptococcus suis type 2 can produce extracellular proteases, which may cleave hemagglutinin to enhance the infection ability of swine influenza virus. the current study investigated whether extracellular proteolytic culture supernatant of streptococcus suis type 2, isolated from jiangsu, enhanced the infection abili ...200818557523
development of reverse transcription loop-mediated isothermal amplification for rapid detection of h9 avian influenza virus.reverse transcription loop-mediated isothermal amplification (rt-lamp) is a unique gene amplification method that can be completed within 45 min at 63 degrees c. in this study, rt-lamp was used to develop a rapid and sensitive laboratory diagnostic system for the h9 subtype of avian influenza virus (aiv). the experiment results from the reference strains demonstrated that the established rt-lamp sensitivity was 10-fold higher than that of rt-pcr, with the detection limit of 10 copies per reactio ...200818572258
phylogenetic analysis of swine influenza viruses recently isolated in korea.several influenza a viral subtypes were isolated from pigs during a severe outbreak of respiratory disease in korea during 2005 and 2006. they included a classical swine h1n1 subtype, two swine-human-avian triple-recombinant h1n2 subtypes, and a swine-human-avian triple-recombinant h3n2 subtype. in the current study, genetic characterization to determine the probable origin of these recent isolates was carried out for the first time. phylogenetic analysis indicated that all the recent korean iso ...200818574682
influenza virus protecting rna: an effective prophylactic and therapeutic antiviral.another influenza pandemic is inevitable, and new measures to combat this and seasonal influenza are urgently needed. here we describe a new concept in antivirals based on a defined, naturally occurring defective influenza virus rna that has the potential to protect against any influenza a virus in any animal host. this "protecting rna" (244 rna) is incorporated into virions which, although noninfectious, deliver the rna to those cells of the respiratory tract that are naturally targeted by infe ...200818579602
comparison of the clinical effectiveness of oseltamivir and zanamivir against influenza virus infection in children.we compared the clinical effectiveness of oseltamivir and zanamivir in children with influenza a (h1n1) virus, influenza a (h3n2) virus, and influenza b virus infections.200818582202
[phylogenetic analysis of human/swine/avian gene reassortant h1n2 influenza a virus isolated from a pig in china].our aim in this study was to determine the genetic characterization and probable origin of the h1n2 swine influenza virus (a/swine/guangxi/13/2006) (sw/gx/13/06) from lung tissue of a pig in guangxi province, china.200818590231
comparison of three serological assays to determine the cross-reactivity of antibodies from eight genetically diverse u.s. swine influenza viruses.swine influenza virus is an economically important pathogen to the u.s. swine industry. new influenza subtypes and isolates within subtypes with different genetic and antigenic makeup have recently emerged in u.s. swineherds. as a result of the emergence of these new viruses, diagnosticians' ability to accurately diagnose influenza infection in pigs and develop appropriate vaccine strategies has become increasingly difficult. the current study compares the ability of subtype-specific commercial ...200818599846
seasonal inactivated influenza virus vaccines.inactivated influenza virus vaccines are the primary modality used for prevention of influenza. a system of annual identification of new strains causing illnesses, selections for vaccines, chick embryo growth, inactivation, processing, packaging, distribution and usage has been in place for decades. current vaccines contain 15 microg of the ha of an a/h1n1, a/h3n2 and b strain and are given parenterally to induce serum anti-ha antibody for prevention of subsequent infection and illness from natu ...200818602728
cross-subtype immunity against avian influenza in persons recently vaccinated for influenza.avian influenza virus (h5n1) can be transmitted to humans, resulting in a severe or fatal disease. the aim of this study was to evaluate the immune cross-reactivity between human and avian influenza (h5n1) strains in healthy donors vaccinated for seasonal influenza a (h1n1)/(h3n2). a small frequency of cd4 t cells specific for subtype h5n1 was detected in several persons at baseline, and seasonal vaccine administration enhanced the frequency of such reactive cd4 t cells. we also observed that se ...200818258091
adamantane-resistant influenza infection during the 2004-05 season.adamantane-resistant influenza a is an emerging problem, but infections caused by resistant and susceptible viruses have not been compared. we identified adamantane resistance in 47% of 152 influenza a virus (h3n2) isolates collected during 2005. resistant and susceptible viruses caused similar symptoms and illness duration. the prevalence of resistance was highest in children.200818258102
adamantane resistance in circulating human influenza a viruses from alberta, canada (1970-2007).mutation in one of five key amino acid residues (positions 26, 27, 30, 31 and 34) within the m2 protein of influenza a viruses, leads to resistance against the adamantane class of anti-influenza drugs. to investigate the emergence and prevalence of adamantane resistance in alberta, canada (between 1970 and 2007), 381 influenza a positive samples (original patient specimens) or isolates (virus cultured from patient specimens) were analyzed for changes in these critical amino acid residues. our re ...200818258311
chicken lung lectin is a functional c-type lectin and inhibits haemagglutination by influenza a virus.many proteins of the calcium-dependent (c-type) lectin family have been shown to play an important role in innate immunity. they can bind to a broad range of carbohydrates, which enables them to interact with ligands present on the surface of micro-organisms. we previously reported the finding of a new putative chicken lectin, which was predominantly localized to the respiratory tract, and thus termed chicken lung lectin (cll). in order to investigate the biochemical and biophysical properties o ...200818261862
cloning, expression and immunoassay detection of ferret ifn-gamma.ferrets (mustela putorius furo) develop symptoms upon influenza infection that resemble those of humans, including sneezing, body temperature variation and weight loss. highly pathogenic strains of influenza a, such as h5n1, have the capacity to cause severe illness or death in ferrets. the use of ferrets as a model of influenza infection is currently limited by a lack of species-specific immunological reagents. interferon gamma (ifn-gamma) plays a key role in the development of innate and adapt ...200818262264
prediction of mutations in h3n2 hemagglutinins of influenza a virus from north america based on different datasets.with rapid increase in influenza a virus database, an important issue is whether the predictions are similar based on different datasets. here we stratify 482 h3n2 hemagglutinins from influenza a virus in north america to different datasets. the predictions are made using logistic regression. the results show that the different datasets have significant impact on the predictions.200818289106
design, synthesis, inhibitory activity, and sar studies of hydrophobic p-aminosalicylic acid derivatives as neuraminidase inhibitors.a series of hydrophobic p-aminosalicylic acid derivatives containing a lipophilic side chain at c-2 and an amino or guanidine at c-5 were synthesized and evaluated for their ability to inhibit neuraminidase (na) of influenza a virus (h3n2). all compounds were synthesized in good yields starting from commercially available p-aminosalicylic acid (pas) using a suitable synthetic strategy. these compounds showed potent inhibitory activity against influenza a na. within this series, six compounds, 11 ...200818304821
spatial epidemiology of an h3n2 swine influenza outbreak.the h3n2 swine influenza virus appeared for the 1st time in the province of manitoba during the fall of 2004. the purpose of this study was to characterize how swine influenza moved through the province in time and space, and to determine if there are any significant patterns associated with this movement. herds with outbreaks of h3n2 swine influenza were located by using a geographic information system and analyzed by using spatial analysis software. descriptive and spatial statistics, includin ...200818309747
in vitro inhibition of human influenza a virus infection by fruit-juice concentrate of japanese plum (prunus mume sieb. et zucc).using a plaque reduction assay, treatment of human influenza a viruses with the fruit-juice concentrate of japanese plum (prunus mume sieb. et zucc) showed strong in vitro anti-influenza activity against human influenza a viruses before viral adsorption, but not after viral adsorption, with 50% inhibitory concentration (ic50) values against a/pr/8/34 (h1n1) virus, a/aichi/2/68 (h3n2) virus and a/memphis/1/71 (h3n2) virus of 6.35+/-0.17, 2.84+/-1.98 and 0.53+/-0.10 microg/ml, respectively. the pl ...200818310920
influenza a virus neuraminidase limits viral superinfection.enveloped viruses use multiple mechanisms to inhibit infection of a target cell by more than one virion. these mechanisms may be of particular importance for the evolution of segmented viruses, because superinfection exclusion may limit the frequency of reassortment of viral genes. here, we show that cellular expression of influenza a virus neuraminidase (na), but not hemagglutinin (ha) or the m2 proton pump, inhibits entry of ha-pseudotyped retroviruses. cells infected with h1n1 or h3n2 influen ...200818321971
[construction and immunogenicity analysis of antigenic epitopes of swine influenza virus].several antigen epitopes were designed according to the sequences of swine influenza virus hemagglutinin (ha) genes and lined with the interval. the gene was amplified by pcr and sub cloned into pet30a (+) vector. the fusion protein was expressed in e. coli bl21 (de3) by induced with iptg and purified by affinity chromatography. the molecular weight of the protein was about 20 kd in sds-page. immunological activity of the fusion protein was analyzed by western blot. the results showed that the f ...200818616184
domestic pigs have low susceptibility to h5n1 highly pathogenic avian influenza viruses.genetic reassortment of h5n1 highly pathogenic avian influenza viruses (hpai) with currently circulating human influenza a strains is one possibility that could lead to efficient human-to-human transmissibility. domestic pigs which are susceptible to infection with both human and avian influenza a viruses are one of the natural hosts where such reassortment events could occur. virological, histological and serological features of h5n1 virus infection in pigs were characterized in this study. two ...200818617994
outbreaks of influenza a among nonvaccinated healthcare workers: implications for resource-limited settings.we identified 3 outbreaks of influenza a (attack rates, 18%-24%) among thai healthcare workers in intensive care units. all outbreaks were epidemiologically linked to an index patient with pneumonia due to influenza a virus (subtype h3n2). the investigations of these outbreaks incurred costs that exceeded the estimated costs of healthcare worker influenza vaccination by more than 10-fold.200818624648
surveillance for neuraminidase inhibitor resistance among human influenza a and b viruses circulating worldwide from 2004 to 2008.the surveillance of seasonal influenza virus susceptibility to neuraminidase (na) inhibitors was conducted using an na inhibition assay. the 50% inhibitory concentration values (ic(50)s) of 4,570 viruses collected globally from october 2004 to march 2008 were determined. based on mean ic(50)s, a(h3n2) viruses (0.44 nm) were more sensitive to oseltamivir than a(h1n1) viruses (0.91 nm). the opposite trend was observed with zanamivir: 1.06 nm for a(h1n1) and 2.54 nm for a(h3n2). influenza b viruses ...200818625765
structure-activity relationship of flavonoids as influenza virus neuraminidase inhibitors and their in vitro anti-viral activities.flavonoids are polyphenolic compounds that widely exist in plant kingdom, and the structure-activity relationship (sar) of 25 flavonoids was studied on neuraminidase (na) activity of influenza virus. three typical influenza virus strains a/pr/8/34 (h1n1), a/jinan/15/90 (h3n2), and b/jiangshu/10/2003 were used as the source of nas, the average of ic(50)s of these compounds on these nas was used in the sar analysis. the order of potency for na inhibition was as follows: aurones>flavon(ol)es>isofla ...200818640042
seasonality of influenza a(h3n2) virus: a hong kong perspective (1997-2006).the underlying basis for the seasonality of influenza a viruses is still uncertain. phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from southeast asia.200818648550
influenza guideline for south africa--update 2008.objective: the south african thoracic society, in conjunction with interested stakeholders, published a guideline for influenza management in adults in 1999. this year the south african thoracic society (sats) identified the need to revise that guideline for the following reasons: * to indicate the viral strains that are to be incorporated into the vaccine for the 2008 season * to add important new data regarding treatment of influenza * to add a section on influenza in children * to clarify iss ...200818652399
an improved embryonated chicken egg model for the evaluation of antiviral drugs against influenza a virus.influenza is a serious global public health problem and an economic burden. with the continual emergence of new influenza a virus strains, new antiviral drugs are needed urgently. in this study, an improved embryonated chicken egg model for evaluating antiviral activity against influenza a virus was developed. in the model, the influenza a virus was injected into the allantoic cavity and ribavirin was injected into the albumen of the egg. the levels of influenza a virus in the allantoic fluid wa ...200818652846
modeling amantadine treatment of influenza a virus in vitro.we analyzed the dynamics of an influenza a/albany/1/98 (h3n2) viral infection, using a set of mathematical models highlighting the differences between in vivo and in vitro infection. for example, we found that including virion loss due to cell entry was critical for the in vitro model but not for the in vivo model. experiments were performed on influenza virus-infected mdck cells in vitro inside a hollow-fiber (hf) system, which was used to continuously deliver the drug amantadine. the hf system ...200818653201
[investigation of prophylactic activity of ingavirin, a new russian drug, against grippe a virus (h3n2)].antiviral efficacy of ingavirin was studied on albino mice infected intranasally by the grippe a virus (h3n2) vs. tamiflu, remantadin and arbidol. ingavirin used prophylactically in doses of 5 to 10 mg/kg was shown to be effective in protecting the animals from death and inhibiting the specific hemagglutinin formation and the virus reproduction in the lungs (by the accumulation).200819441652
single mutation induced h3n2 hemagglutinin antibody neutralization: a free energy perturbation study.the single mutation effect on the binding affinity of h3n2 viral protein hemagglutinin (ha) with the monoclonical antibody fragment (fab) is studied in this paper using the free energy perturbation (fep) simulations. an all-atom protein model with explicit solvents is used to perform an aggregate of several microsecond fep molecular dynamics simulations. a recent experiment shows that a single mutation in h3n2 ha, t131i, increases the antibody-antigen dissociation constant kd by a factor of appr ...200819367871
study of efficiency of therapeutic and preventive anaferon (pediatric formulation) in mice with influenza infection.therapeutic and preventive treatment of mice intranasally infected with a lethal dose of a/aichi/2/68 (h3n2) influenza virus with anaferon (pediatric formulation) demonstrated an antiviral effect of the drug (increased percent of survivors and prolonged lifespan).200819513378
a vaccine manufacturer's approach to address medical needs related to seasonal and pandemic influenza viruses.vaccination is considered to be one of the most effective tools to decrease morbidity as well as mortality caused by influenza viruses. for the prevention of seasonal influenza, fluarix and flulaval have been marketed since 1987 and 1992, respectively. both vaccines have consistently been shown to meet or exceed the regulatory criteria for immunogenicity against the three strains h1n1, h3n2 and b, have a good safety profile, and are recommended for vaccinating children and adults of all ages. fo ...200819453402
influenza vaccine strain selection and recent studies on the global migration of seasonal influenza viruses.annual influenza epidemics in humans affect 5-15% of the population, causing an estimated half million deaths worldwide per year [stohr k. influenza-who cares. lancet infectious diseases 2002;2(9):517]. the virus can infect this proportion of people year after year because the virus has an extensive capacity to evolve and thus evade the immune response. for example, since the influenza a(h3n2) subtype entered the human population in 1968 the a(h3n2) component of the influenza vaccine has had to ...200819230156
animal influenza epidemiology.influenza a viruses exist within their natural host, aquatic birds, in a number of antigenic subtypes. only a few of these subtypes have successfully crossed into other avian and mammalian hosts. this brief review will focus on just three examples of viruses that have successfully passed between species; avian h5ni1 and h9n2 viruses and h3n2 viruses which have transmitted from aquatic birds to humans and then to swine. although there are a number of other subtypes that have also transmitted succ ...200819230163
heterosubtypic t-cell responses against avian influenza h5 haemagglutinin are frequently detected in individuals vaccinated against or previously infected with human subtypes of influenza.cellula r immune responses play a critical role in providing help for the production of neutralizing antibodies to influenza virus, as well as producing anti-viral cytokines and killing infected cells in the lung. heterosubtypic t-cell responses between different subtypes of influenza have been shown to exist in humans and to provide protection against morbidity and mortality associated with h5n1 infection in animal challenge models. therefore, existing t-cell responses induced by natural infect ...200819453462
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