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a synthetic influenza virus vaccine induces a cellular immune response that correlates with reduction in symptomatology and virus shedding in a randomized phase ib live-virus challenge in humans.current influenza vaccines elicit primarily antibody-based immunity. they require yearly revaccination and cannot be manufactured until the identification of the circulating viral strain(s). these issues remain to be addressed. here we report a phase ib trial of a vaccine candidate (flu-v) eliciting cellular immunity. thirty-two males seronegative for the challenge virus by hemagglutination inhibition assay participated in this single-center, randomized, double-blind study. volunteers received o ...201525994549
environmental conditions affect exhalation of h3n2 seasonal and variant influenza viruses and respiratory droplet transmission in ferrets.the seasonality of influenza virus infections in temperate climates and the role of environmental conditions like temperature and humidity in the transmission of influenza virus through the air are not well understood. using ferrets housed at four different environmental conditions, we evaluated the respiratory droplet transmission of two influenza viruses (a seasonal h3n2 virus and an h3n2 variant virus, the etiologic virus of a swine to human summertime infection) and concurrently characterize ...201525969995
serological evidence of equine influenza infections among persons with horse exposure, iowa.equine influenza virus (eiv) is considered enzootic in north america and experimental studies have documented human eiv infections.201525959164
investigation of an outbreak of variant influenza a(h3n2) virus infection associated with an agricultural fair-ohio, august 2012.in 2012, one third of cases in a multistate outbreak of variant influenza a(h3n2) virus ([h3n2]v) infection occurred in ohio. we conducted an investigation of (h3n2)v cases associated with agricultural fair a in ohio.201525948864
[analysis of influenza a/h3n2 neuraminidase genes obtained from influenza patients in the 2011/12 and 2012/13 seasons in japan].influenza virus has neuraminidase (na), a surface protein with enzymatic activity that is essential for virus replication. mutation may affect the effectiveness of na inhibitors that are used for the treatment of influenza patients. in this study, we determined the na gene sequences from the clinical isolates of influenza patients to examine the chronological genetic changes and the relation to drug susceptibility.201525942938
dynamics of influenza seasonality at sub-regional levels in india and implications for vaccination timing.influenza surveillance is an important tool to identify emerging/reemerging strains, and defining seasonality. we describe the distinct patterns of circulating strains of the virus in different areas in india from 2009 to 2013.201525938466
computational characterization of transient strain-transcending immunity against influenza a.the enigmatic observation that the rapidly evolving influenza a (h3n2) virus exhibits, at any given time, a limited standing genetic diversity has been an impetus for much research. one of the first generative computational models to successfully recapitulate this pattern of consistently constrained diversity posits the existence of a strong and short-lived strain-transcending immunity. building on that model, we explored a much broader set of scenarios (parameterizations) of a transient strain- ...201525933195
genetic changes in influenza a(h3n2) viruses circulating during 2011 to 2013 in northern india (lucknow).genetic variability in the hemagglutinin (ha1) and the neuraminidase (na) genes of influenza viruses results in the emergence of new strains which differ in pathogenicity and severity. the present study was undertaken for genotypic characterization of the ha1 and na genes of the influenza a(h3n2) strains, detected during the 2011-2013. a total of fifty five influenza a(h3n2) positive samples [2011 (n = 20), 2012 (n = 4) and 2013 (n = 31)] were studied. the 824 bp segment of ha1 gene and 931 bp s ...201525914198
colorimetric detection of influenza a virus using antibody-functionalized gold nanoparticles.early and accurate diagnosis is considered the key issue to prevent the further spread of viruses and facilitate influenza therapy. herein, we report a colorimetric immunosensor for influenza a virus (iav) based on gold nanoparticles (aunps) modified with monoclonal anti-hemagglutinin antibody (mab). the immunosensor allows for a fast, simple, and selective detection of iav. in this assay, influenza-specific antibodies are conjugated to aunps to create mab-aunp probes. since iav has multiple rec ...201525899840
[eficient inhibition of human influenza a virus by oligonucleotides electrostatically fixed on polylysine-containing tio2 nanoparticles].antiviral activity of tio2 * pl * dna nanobiocomposites was studied on the mdck cell culture infected with influenza a virus (subtype h3n2). dna fragments in the nanocomposites are electrostatically bound to titanium dioxide nanoparticles pre-covered with polylysine. it was shown that tio2 * pl * dna(v3') nanocomposite bearing the dna(v3') fragment targeted to the 3'-end of the noncoding region of segment 5 of viral rna specifically inhibited the virus reproduction with the efficiency of 99.8 an ...201525895339
selecting vaccine strains for h3n2 human influenza a virus.h3n2 human influenza a virus causes epidemics of influenza mainly in the winter season in temperate regions. since the antigenicity of this virus evolves rapidly, several attempts have been made to predict the major amino acid sequence of hemagglutinin 1 (ha1) in the target season of vaccination. however, the usefulness of predicted sequence was unclear because its relationship to the antigenicity was unknown. here the antigenic model for estimating the degree of antigenic difference (antigenic ...201525893173
respiratory viruses and torque teno virus in adults with acute respiratory infections.to define the molecular epidemiology of respiratory viral infections in adult patients.201525890989
monoclonal antibody specific to ha2 glycopeptide protects mice from h3n2 influenza virus infection.canine influenza virus (civ) subtype h3n2 is a newly identified, highly contagious respiratory pathogen that causes cough, pneumonia and other respiratory symptoms in dogs. data indicate that the virus is responsible for recent clinical cases of dog disease in china. however, therapeutic options for this disease are very limited. in this study, seven monoclonal antibodies (mabs) against civ js/10 (an h3n2 subtype virus) were produced and characterized. among them, mab d7, which is specific for t ...201525888728
global and quantitative proteomic analysis of dogs infected by avian-like h3n2 canine influenza virus.canine influenza virus a (h3n2) is a newly emerged etiological agent for respiratory infections in dogs. the mechanism of interspecies transmission from avian to canine species and the development of diseases in this new host remain to be explored. to investigate this, we conducted a differential proteomics study in 2-month-old beagles inoculated intranasally with 10(6) tcid50 of a/canine/guangdong/01/2006 (h3n2) virus. lung sections excised at 12 h post-inoculation (hpi), 4 days, and 7 days pos ...201525883591
lower seroreactivity to european than to north american h3n2 swine influenza viruses in humans, luxembourg, 2010.seroreactivity to h3n2 swine influenza viruses (sivs)was evaluated in serum samples collected from 843 people aged 0 to 100 years in 2010 in luxembourg.sera were analysed by haemagglutination inhibition(hi) and virus neutralisation (vn) assays targeting a european h3n2 siv, a north american h3n2 variant of swine origin (h3n2v) and human seasonal h3n2 viruses isolated in 1975, 1995 and 2005. hi antibodies(titre ≥ 10) against european h3n2 siv were almost exclusively detected in those born before ...201525860393
the repeated introduction of the h3n2 virus from human to swine during 1979-1993 in china.limited data are available regarding the swine influenza viruses (sivs) that circulated in mainland china prior to the 1990s. eleven h3n2 virus strains were isolated from swine populations from 1979 to 1992. to determine the origin and tendency of these sivs, the phylogenetic and antigenic properties of these viruses were analyzed based on the whole genome sequenced and the hi titrations with post-infection ferret antisera against influenza a (h3n2) virus isolates of swine and human origin. the ...201525858119
intrahost dynamics of antiviral resistance in influenza a virus reflect complex patterns of segment linkage, reassortment, and natural selection.resistance following antiviral therapy is commonly observed in human influenza viruses. although this evolutionary process is initiated within individual hosts, little is known about the pattern, dynamics, and drivers of antiviral resistance at this scale, including the role played by reassortment. in addition, the short duration of human influenza virus infections limits the available time window in which to examine intrahost evolution. using single-molecule sequencing, we mapped, in detail, th ...201525852163
antiviral activity of a nanoemulsion of polyprenols from ginkgo leaves against influenza a h3n2 and hepatitis b virus in vitro.in order to improve the bioavailability levels of polyprenols (derived from ginkgo leaves (gbp)) in the human body, a gbp nanoemulsion was prepared, and its antiviral activity was evaluated against influenza a h3n2 and hepatitis b virus in vitro.201525808155
vaccination-challenge studies with a port chalmers/73 (h3n2)-based swine influenza virus vaccine: reflections on vaccine strain updates and on the vaccine potency test.the human a/port chalmers/1/73 (h3n2) influenza virus strain, the supposed ancestor of european h3n2 swine influenza viruses (sivs), was used in most commercial siv vaccines in europe until recently. if manufacturers want to update vaccine strains, they have to perform laborious intratracheal (it) challenge experiments and demonstrate reduced virus titres in the lungs of vaccinated pigs. we aimed to examine (a) the ability of a port chalmers/73-based commercial vaccine to induce cross-protection ...201525804707
mitochondrial antiviral signaling adaptor mediated apoptosis in h3n2 swine influenza virus infection is inhibited by viral protein ns1 in vitro.we investigated the in vitro role of mitochondrial antiviral signaling adaptor (mavs) in apoptosis induced by h3n2 swine influenza virus infection and the influence of viral ns1 (nonstructural protein 1) protein on this process. h3n2 swine influenza virus (siv, a/swine/shandong/3/2005) was co-cultured with human lung epithelial a549 cells. the relationship of mavs expression to siv replication and apoptosis, and the influence of viral proteins on mavs functions were studied. the data indicate th ...201525800220
analysis of cytokine production in a newly developed canine tracheal epithelial cell line infected with h3n2 canine influenza virus.the madin-darby canine kidney (mdck) cell line is typically used to analyze pathological features after canine influenza virus (civ) infection. however, mdck cells are not the ideal cell type, because they are kidney epithelial cells. therefore, we generated an immortalized canine tracheal epithelial cell line, ku-cbe, to more reliably study immune responses to civ infection in the respiratory tract. ku-cbe cells expressed the influenza virus receptor, α-2,3-sialic acid (sa), but not α-2,6-sa. k ...201525797195
with flu numbers among staff increasing, hospitals report challenges, need for vigilance.with a flu vaccine that is largely missing the mark, eds around the country have their hands full with patients complaining of flu-like symptoms. the flu arrived earlier this year than usual, and by mid-january, it was still not clear whether the virus had peaked. many eds are struggling with staffing challenges as more personnel than usual are missing work because they have come down with the flu themselves. as a result, hospital administrators are stepping up infection control practices and ur ...201525793248
population susceptibility to a variant swine-origin influenza virus a(h3n2) in vietnam, 2011-2012.a reassortant swine-origin a(h3n2) virus (a/swine/binhduong/03-9/2010) was detected through swine surveillance programmes in southern vietnam in 2010. this virus contains haemagglutinin and neuraminidase genes from a human a(h3n2) virus circulating around 2004-2006, and the internal genes from triple-reassortant swine influenza a viruses (iavs). to assess population susceptibility to this virus we measured haemagglutination inhibiting (hi) titres to a/swine/binhduong/03-9/2010 and to seasonal a/ ...201525761949
safety and immunogenicity of influenza whole inactivated virus vaccines: a phase i randomized clinical trial.influenza vaccine production capacity is still insufficient to meet global demand in case of a pandemic. to expand worldwide influenza vaccine production capacity, a solid and transferable egg-based influenza vaccine production process was established that is suitable for upscaling and technology transfer to vaccine manufacturers in low- and middle-income countries. as a proof-of-concept, the safety and immunogenicity of a pandemic whole inactivated virus (wiv) vaccine (h5n1) and a monovalent se ...201525751506
whole-genome sequences of influenza a(h3n2) viruses isolated from brazilian patients with mild illness during the 2014 season.the influenza a(h3n2) virus has circulated worldwide for almost five decades and is the dominant subtype in most seasonal influenza epidemics, as occurred in the 2014 season in south america. in this study we evaluate five whole genome sequences of influenza a(h3n2) viruses detected in patients with mild illness collected from january-march 2014. to sequence the genomes, a new generation sequencing (ngs) protocol was performed using the ion torrent pgm platform. in addition to analysing the comm ...201525742277
origins and evolutionary dynamics of h3n2 canine influenza virus.influenza a viruses (iavs) are maintained mainly in wild birds, and despite frequent spillover infections of avian iavs into mammals, only a small number of viruses have become established in mammalian hosts. a new h3n2 canine influenza virus (civ) of avian origin emerged in asia in the mid-2000s and is now circulating in dog populations of china and south korea, and possibly in thailand. the emergence of civ provides new opportunities for zoonotic infections and interspecies transmission. we ex ...201525740996
estimating the life course of influenza a(h3n2) antibody responses from cross-sectional data.the immunity of a host population against specific influenza a strains can influence a number of important biological processes, from the emergence of new virus strains to the effectiveness of vaccination programmes. however, the development of an individual's long-lived antibody response to influenza a over the course of a lifetime remains poorly understood. accurately describing this immunological process requires a fundamental understanding of how the mechanisms of boosting and cross-reactivi ...201525734701
comparison of the performance of 2 commercial multiplex pcr platforms for detection of respiratory viruses in upper and lower tract respiratory specimens.the performance of the clart® pneumovir system with that of the luminex xtag rvp fast v1 assay for detection of most common respiratory viruses in upper and lower tract respiratory specimens (n=183) from unique patients with influenza-like syndrome or lower tract respiratory infection. nested pcr coupled to automated sequencing was used for resolution of discrepancies. fully concordant results were obtained for a total of 122 specimens, whereas 56 specimens gave partially (n=21) or fully discord ...201525724853
optimization of an enzyme-linked lectin assay suitable for rapid antigenic characterization of the neuraminidase of human influenza a(h3n2) viruses.antibodies to neuraminidase (na), the second most abundant surface protein of the influenza virus, contribute to protection against influenza virus infection. although traditional and miniaturized thiobarbituric acid (tba) neuraminidase inhibition (ni) assays have been successfully used to characterize the antigenic properties of na, these methods are cumbersome and not easily amendable to rapid screening. an additional difficulty of the ni assay is the interference by hemagglutinin (ha)-specifi ...201525712563
challenges in antigenic characterization of circulating influenza a(h3n2) viruses during the 2011-2012 influenza season: an ongoing problem?genetic and antigenic characterization of 37 representative influenza a(h3n2) virus strains isolated in greece during the 2011-2012 winter season was performed to evaluate matching of the viruses with the seasonal influenza vaccine strain a/perth/16/2009. hemagglutinin gene sequence analysis revealed that all greek strains clustered within the victoria/208 genetic clade. furthermore, substitutions in the antigenic and glycosylation sites suggested potential antigenic drift. our hemagglutination ...201525694524
expression of h3n2 nucleoprotein in maize seeds and immunogenicity in mice.oral administration of maize-expressed h3n2 nucleoprotein induced antibody responses in mice showing the immunogenicity of plant-derived antigen and its potential to be utilized as a universal flu vaccine. influenza a viruses cause influenza epidemics that are devastating to humans and livestock. the vaccine for influenza needs to be reformulated every year to match the circulating strains due to virus mutation. influenza virus nucleoprotein (np) is a multifunctional rna-binding protein that is ...201525677970
a mutant h3n2 influenza virus uses an alternative activation mechanism in tmprss2 knockout mice by loss of an oligosaccharide in the hemagglutinin stalk region.the host protease tmprss2 plays an essential role in proteolytic activation of the influenza a virus (iav) hemagglutinin (ha) protein possessing a monobasic cleavage site. however, after passages in tmprss2 knockout mice, an h3n2 subtype iav began to undergo cleavage activation of ha, showing high virulence in the mice due to the loss of an oligosaccharide at position 8 in the ha stalk region. thus, the h3n2 iav acquired cleavability by an alternative ha activation mechanism/protease(s).201525673722
a(h7n9) virus results in early induction of proinflammatory cytokine responses in both human lung epithelial and endothelial cells and shows increased human adaptation compared with avian h5n1 virus.similar to h5n1 viruses, a(h7n9) influenza viruses have been associated with severe respiratory disease and fatal outcomes in humans. while high viral load, hypercytokinemia, and pulmonary endothelial cell involvement are known to be hallmarks of h5n1 virus infection, the pathogenic mechanism of the a(h7n9) virus in humans is largely unknown. in this study, we assessed the ability of a(h7n9) virus to infect, replicate, and elicit innate immune responses in both human bronchial epithelial cells a ...201525673714
emergence of human-like h3n2 influenza viruses in pet dogs in guangxi, china.after the 1968 h3n2 pandemic emerged in humans, h3n2 influenza viruses continuously circulated and evolved in nature. an h3n2 variant was circulating in humans in the 1990s and subsequently introduced into the pig population in the 2000s. this virus gradually became the main subtype of swine influenza virus worldwide. however, there were no reports of infections in dogs with this virus.201525645259
limited effect of recombinant human mannose-binding lectin on the infection of novel influenza a (h7n9) virus in vitro.mannose-binding lectin (mbl), a pattern-recognition molecule in serum, recognizes specific hexose sugars rich in mannose and n-acetylglucosamine on bacterium, yeasts, viruses as well as apoptotic cells. it has been well-identified that mbl has antiviral effects via binding to seasonal influenza h1 and h3 subtype viruses. influenza a (h7n9) virus, a novel reassortant virus to human population, possesses the surface hemagglutinin (ha) and neuraminidase (na) genes from duck and wild-bird influenza ...201525634695
whole-genome sequences of influenza a(h3n2) viruses isolated from brazilian patients with mild illness during the 2014 season.the influenza a(h3n2) virus has circulated worldwide for almost five decades and is the dominant subtype in most seasonal influenza epidemics, as occurred in the 2014 season in south america. in this study we evaluate five whole genome sequences of influenza a(h3n2) viruses detected in patients with mild illness collected from january-march 2014. to sequence the genomes, a new generation sequencing (ngs) protocol was performed using the ion torrent pgm platform. in addition to analysing the comm ...201525626457
structure and receptor binding preferences of recombinant human a(h3n2) virus hemagglutinins.a(h3n2) influenza viruses have circulated in humans since 1968, and antigenic drift of the hemagglutinin (ha) protein continues to be a driving force that allows the virus to escape the human immune response. since the major antigenic sites of the ha overlap into the receptor binding site (rbs) of the molecule, the virus constantly struggles to effectively adapt to host immune responses, without compromising its functionality. here, we have structurally assessed the evolution of the a(h3n2) viru ...201525617824
identification of pb2 mutations responsible for the efficient replication of h5n1 influenza viruses in human lung epithelial cells.highly pathogenic h5n1 avian influenza viruses have caused outbreaks among poultry worldwide, resulting in sporadic infections in humans with approximately 60% mortality. however, efficient transmission of h5n1 viruses among humans has yet to occur, suggesting that further adaptation of h5n1 viruses to humans is required for their efficient transmission among humans. the viral determinants for efficient replication in humans are currently poorly understood. here, we report that the polymerase pb ...201525609813
early estimates of seasonal influenza vaccine effectiveness - united states, january 2015.in the united states, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months. each season since 2004-05, cdc has estimated the effectiveness of seasonal influenza vaccine in preventing medically attended acute respiratory illness (ari) associated with laboratory-confirmed influenza. this season, early estimates of influenza vaccine effectiveness are possible because of widespread, early circulation of influenza viruses. by january 3, 2015, 46 states were expe ...201525590680
detection of a transient r292k mutation in influenza a/h3n2 viruses shed for several weeks by an immunocompromised patient.we describe the case of an immunocompromised patient, positive for influenza a virus (h3n2), in whom the neuraminidase r292k mutation was transiently detected during oseltamivir treatment. the r292k mutation was identified by direct testing in 3 of 11 respiratory specimens collected throughout the patient's illness but in none of the cultures from those specimens.201525588658
serological evidence of avian influenza virus and canine influenza virus infections among stray cats in live poultry markets, china.from january 2010 to january 2012, we collected sera samples from 700 stray cats living in close proximity to poultry farms or poultry markets in 4 provinces in china. a number of cats had evidence of avian and canine influenza virus infection: avian h9n2 [24 by hi ≥1:20 and 16 by microneutralization (mn) assay ≥1:80]; avian h5n1 (9 by hi ≥1:20 and 3 by mn assay ≥1:80) and canine h3n2 (32 by hi ≥1:20 and 18 by mn ≥1:80). bivariate analyses revealed that cats sampled near live poultry markets and ...201525575880
detection of influenza antigenic variants directly from clinical samples using polyclonal antibody based proximity ligation assays.identification of antigenic variants is the key to a successful influenza vaccination program. the empirical serological methods to determine influenza antigenic properties require viral propagation. here a novel quantitative pcr-based antigenic characterization method using polyclonal antibody and proximity ligation assays, or so-called polypla, was developed and validated. this method can detect a viral titer that is less than 1000 tcid50/ml. not only can this method differentiate between diff ...201525546251
safety and immunogenicity of cell culture-derived a/h3n2 variant influenza vaccines: a phase i randomized, observer-blind, dose-ranging study.a/h3n2 variant (h3n2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important.201525538277
chimeric neuraminidase and mutant pb1 gene constellation improves growth and yield of h5n1 vaccine candidate virus.we previously showed that a mutated pb1 gene improved the growth kinetics of a h3n2 influenza reassortant. here, we showed that the same mutations improved the growth kinetics of a virus containing the a/vietnam/1203/2004 (h5n1) haemagglutinin and neuraminidase (na). total protein yield and na activity were increased when a chimeric na was included. these increases indicated that the synergistic effect was due to the gene constellation containing both the altered pb1 gene and the chimeric na gen ...201525502649
episodic nucleotide substitutions in seasonal influenza virus h3n2 can be explained by stochastic genealogical process without positive selection.nucleotide substitutions in the ha1 domain of seasonal influenza virus h3n2 occur in temporal clusters, which was interpreted as a result of recurrent selective sweeps underlying antigenic drift. however, classical theory by watterson suggests that episodic substitutions are mainly due to stochastic genealogy combined with unique genetic structure of influenza virus: high mutation rate over a nonrecombining viral segment. this explains why even larger variance in the number of allelic fixations ...201525492497
efficient replication and strong induction of innate immune responses by h9n2 avian influenza virus in human dendritic cells.avian influenza a (h9n2) viruses have occasionally been identified in humans with upper respiratory tract infections. the novel h7n9/2013 virus identified in china shows that a low pathogenic avian influenza (lpai) virus can be highly pathogenic in humans. therefore, it is important to understand virus-host cell interactions and immune responses triggered by lpai viruses in humans. we found that lpai a/hong kong/1073/99 (h9n2) virus replicated efficiently in human dendritic cells (dcs). the h9n2 ...201425461529
rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.live attenuated influenza vaccine viruses (laivs) can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated master donor virus (mdv) and a seasonal wild-type (wt) virus. the vaccine candidates contain hemagglutinin (ha) and neuraminidase (na) genes derived from the circulating wt viruses and the remaining six genes derived from the mdv strains. rapid, efficient selection of the viruses with 6∶2 genome compositions from the large numb ...201424647786
synthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1h)-ones.a target-free approach was applied to discover anti-influenza viral compounds, where influenza infected madin-darby canine kidney cells were treated 7500 different small organic chemicals individually and reduction of virus-induced cytopathic effect was measured. one of the hit compounds was (z)-1-((5-fluoro-1h-indol-3-yl)methylene)-6-methyl-4-thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1h)-one (15a) with half-maximal effective concentrations of 17.4-21.1μm against influenza a/h1n1, a/h3n2 and b viru ...201424794525
aminoadamantanes with persistent in vitro efficacy against h1n1 (2009) influenza a.a series of 2-adamantanamines with alkyl adducts of various lengths were examined for efficacy against strains of influenza a including those having an s31n mutation in m2 proton channel that confer resistance to amantadine and rimantadine. the addition of as little as one ch2 group to the methyl adduct of the amantadine/rimantadine analogue, 2-methyl-2-aminoadamantane, led to activity in vitro against two m2 s31n viruses a/calif/07/2009 (h1n1) and a/pr/8/34 (h1n1) but not to a third a/ws/33 (h1 ...201424793875
population-based hospitalization burden of influenza a virus subtypes and antigenic drift variants in children in hong kong (2004-2011).we aim to document and analyze influenza hospitalization burden in light of antigenic changes in circulating influenza viruses in hong kong.201424786780
genesis and pathogenesis of the 1918 pandemic h1n1 influenza a virus.the source, timing, and geographical origin of the 1918-1920 pandemic influenza a virus have remained tenaciously obscure for nearly a century, as have the reasons for its unusual severity among young adults. here, we reconstruct the origins of the pandemic virus and the classic swine influenza and (postpandemic) seasonal h1n1 lineages using a host-specific molecular clock approach that is demonstrably more accurate than previous methods. our results suggest that the 1918 pandemic virus originat ...201424778238
molecular characterization of circulating pandemic strains of influenza a virus during 2012 to 2013 in lucknow (india).the pandemic h1n1 strain of influenza a virus [a(h1n1)pdm09] is now well adapted in human populations. however, it is still causing sporadic outbreaks worldwide with different severity. the present study was planned to understand the genetic diversity (based on the ha1 gene) of influenza a(h1n1)pdm09 strains circulating during the post pandemic period. the ha1 gene was selected because the ha1 protein is immunogenic, functions as a receptor binding site and indirectly affects transmission and pa ...201424777528
performance of ehealth data sources in local influenza surveillance: a 5-year open cohort study.there is abundant global interest in using syndromic data from population-wide health information systems--referred to as ehealth resources--to improve infectious disease surveillance. recently, the necessity for these systems to achieve two potentially conflicting requirements has been emphasized. first, they must be evidence-based; second, they must be adjusted for the diversity of populations, lifestyles, and environments.201424776527
managing seasonal influenza: oseltamivir treatment policy in indonesia?to manage cases of avian influenza a/h5n1 virus infection and in anticipation of a pandemic triggered by this virus, indonesia purchased and distributed oseltamivir to the government health facilities. oseltamivir is an antiviral drug that was developed for the treatment of influenza infections. disease surveillance and research suggests that seasonal influenza (a/h1n1, a/h3n2 or b) results in considerable morbidity and mortality in indonesia, where over 15% of influenza-like illness and severe ...201424760811
reassortant swine influenza viruses isolated in japan contain genes from pandemic a(h1n1) 2009.in 2013, three reassortant swine influenza viruses (sivs)-two h1n2 and one h3n2-were isolated from symptomatic pigs in japan; each contained genes from the pandemic a(h1n1) 2009 virus and endemic sivs. phylogenetic analysis revealed that the two h1n2 viruses, a/swine/gunma/1/2013 and a/swine/ibaraki/1/2013, were reassortants that contain genes from the following three distinct lineages: (i) h1 and nucleoprotein (np) genes derived from a classical swine h1 ha lineage uniquely circulating among ja ...201424750464
substantial morbidity and mortality associated with pandemic a/h1n1 influenza in mexico, winter 2013-2014: gradual age shift and severity.a recrudescent wave of pandemic influenza a/h1n1 is underway in mexico in winter 2013-14, following a mild 2012-13 a/h3n2 influenza season. mexico previously experienced several waves of pandemic a/h1n1 activity in spring, summer and fall 2009 and winter 2011-2012, with a gradual shift of influenza-related hospitalizations and deaths towards older ages. here we describe changes in the epidemiology of the 2013-14 a/h1n1 influenza outbreak, relative to previous seasons dominated by the a/h1n1 pand ...201424744975
safety and immunogenicity of a vero cell culture-derived whole-virus h5n1 influenza vaccine in chronically ill and immunocompromised patients.the development of vaccines against h5n1 influenza a viruses is a cornerstone of pandemic preparedness. clinical trials of h5n1 vaccines have been undertaken in healthy subjects, but studies in risk groups have been lacking. in this study, the immunogenicity and safety of a nonadjuvanted cell culture-derived whole-virus h5n1 vaccine were assessed in chronically ill and immunocompromised adults. subjects received two priming immunizations with a clade 1 a/vietnam h5n1 influenza vaccine, and a sub ...201424739978
influenza h1n1pdm-specific maternal antibodies offer limited protection against wild-type virus replication and influence influenza vaccination in ferrets.the objective was to study passively acquired influenza h1n1 pandemic (h1n1pdm) maternal antibody kinetics and its impact on subsequent influenza infection and vaccination in ferrets during an outbreak of the h1n1pdm.201424734293
assessment of seasonality of influenza in swine using field submissions to a diagnostic laboratory in ontario between 2007 and 2012.seasonality of any infectious disease is important for its control and monitoring. while influenza seasonality in people has been evaluated extensively, this question has not been studied well in swine populations.201424725968
epidemiological aspects of influenza a related to climatic conditions during and after a pandemic period in the city of salvador, northeastern brazil.during the influenza pandemic of 2009, the a(h1n1)pdm09, a/h3n2 seasonal and influenza b viruses were observed to be co-circulating with other respiratory viruses. to observe the epidemiological pattern of the influenza virus between may 2009-august 2011, 467 nasopharyngeal aspirates were collected from children less than five years of age in the city of salvador. in addition, data on weather conditions were obtained. indirect immunofluorescence, real-time transcription reverse polymerase chain ...201424714967
il-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires cd4+ t cells for heterosubtypic protection.current influenza vaccines are ineffective against novel viruses and the source or the strain of the next outbreak of influenza is unpredictable; therefore, establishing universal immunity by vaccination to limit the impact of influenza remains a high priority. to meet this challenge, a novel vaccine has been developed using the immunogenic live vaccinia virus as a vaccine vector, expressing multiple h5n1 viral proteins (ha, na, m1, m2, and np) together with il-15 as a molecular adjuvant. previo ...201424706798
mutations flanking the carbohydrate binding site of surfactant protein d confer antiviral activity for pandemic influenza a viruses.we recently reported that a trimeric neck and carbohydrate recognition domain (ncrd) fragment of human surfactant protein d (sp-d), a host defense lectin, with combinatorial substitutions at the 325 and 343 positions (d325a+r343v) exhibits markedly increased antiviral activity for seasonal strains of influenza a virus (iav). the ncrd binds to glycan-rich viral envelope proteins including hemagglutinin (ha). we now show that replacement of d325 with serine to create d325s+r343v provided equal or ...201424705721
a humoral immunity survey following the 2012 influenza season after the ph1n1 pandemic in guangzhou, china.according to pathogenic surveillance data during the first half of 2012, the h3n2 influenza virus was prevalent in guangdong, china, but no pandemic h1n1 (ph1n1) virus was detected. this study aimed to measure the seroprevalence of ph1n1 and h3n2 infection following the influenza epidemic in 2012. we collected serum samples by stratified random sampling in a cross-sectional survey from august, 2012 to october, 2012. antibody titers against h3n2, ph1n1, and influenza b antigens were measured by t ...201424702517
influenza a h1n1 pandemic strain evolution--divergence and the potential for antigenic drift variants.the emergence of a novel a(h1n1) strain in 2009 was the first influenza pandemic of the genomic age, and unprecedented surveillance of the virus provides the opportunity to better understand the evolution of influenza. we examined changes in the nucleotide coding regions and the amino acid sequences of the hemagglutinin (ha), neuraminidase (na), and nucleoprotein (np) segments of the a(h1n1)pdm09 strain using publicly available data. we calculated the nucleotide and amino acid hamming distance f ...201424699432
development of high-throughput liquid chips for respiratory virus detection.diagnosis of viral respiratory tract infections clinically is often nonspecific, and a rapid, high-throughput laboratory technique which can detect major respiratory viruses is desirable.201424697109
phylogeny of spanish swine influenza viruses isolated from respiratory disease outbreaks and evolution of swine influenza virus within an endemically infected farm.in the present study, outbreaks of respiratory disease were investigated for the presence of swine influenza virus (siv). in 14 cases the circulating siv strains were isolated, fully sequenced and compared with other known sivs. the viruses causing the outbreaks belonged to the h1n1 (including human pandemic h1n1), h3n2 and h1n2 subtypes. in 11/14 cases the phylogenetic analyses indicated the occurrence of probable reassortment events. in the second part of the study, the genetic evolution of h1 ...201424685238
protective effect of fluvastatin on influenza virus infection.statins are 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors and have pleiotropic effects. it has been suggested that statins may be a potential treatment during the next influenza pandemic. in a previous study we found that a statin/caffeine combination protects balb/c mice against influenza a, subtypes haemagglutinin type 5 and neuraminidase type 1 (h5n1), h3n2 and h1n1 infection. the effect of statins alone on influenza virus infection, however, is not known. in this study, it was i ...201424676773
association between antibody titers and protection against influenza virus infection within households.previous studies have established that antibody titer measured by the hemagglutination-inhibiting (hai) assay is correlated with protection against influenza virus infection, with an hai titer of 1:40 generally associated with 50% protection.201424676208
protective efficacy of a high-growth reassortant swine h3n2 inactivated vaccine constructed by reverse genetic manipulation.novel reassortant h3n2 swine influenza viruses (swiv) with the matrix gene from the 2009 h1n1 pandemic virus have been isolated in many countries as well as during outbreaks in multiple states in the united states, indicating that h3n2 swiv might be a potential threat to public health. since southern china is the world's largest producer of pigs, efficient vaccines should be developed to prevent pigs from acquiring h3n2 subtype swiv infections, and thus limit the possibility of swiv infection at ...201424675833
low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted h3n2 vaccine strain not antigenic drift in circulating viruses.influenza vaccine effectiveness (ve) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. during the 2012-13 season, however, detailed genotypic and phenotypic characterization shows that low ve was instead related to mutations in the egg-adapted h3n2 vaccine strain rather than antigenic drift in circulating viruses.201424667168
influenza virus h1n1 activates platelets through fcγriia signaling and thrombin generation.platelets play crucial functions in hemostasis and the prevention of bleeding. during h1n1 influenza a virus infection, platelets display activation markers. the platelet activation triggers during h1n1 infection remain elusive. we observed that h1n1 induces surface receptor activation, lipid mediator synthesis, and release of microparticles from platelets. these activation processes require the presence of serum/plasma, pointing to the contribution of soluble factor(s). considering that immune ...201424665136
development of rapid immunochromatographic test for hemagglutinin antigen of h7 subtype in patients infected with novel avian influenza a (h7n9) virus.since human infection with the novel h7n9 avian influenza virus was identified in china in march 2013, the relatively high mortality rate and possibility of human-to-human transmission have highlighted the urgent need for sensitive and specific assays for diagnosis of h7n9 infection.201424647358
purification of vero cell derived live replication deficient influenza a and b virus by ion exchange monolith chromatography.we explored the possibilities for purification of various δns1 live, replication deficient influenza viruses on ion exchange methacrylate monoliths. influenza a δns1-h1n1, δns1-h3n2, δns1-h5n1 and δns1-influenza b viruses were propagated in vero cells and concentrated by tangential flow filtration. all four virus strains adsorbed well to cim qa and cim deae anion exchangers, with cim qa producing higher recoveries than cim deae. δns1-influenza a viruses adsorbed well also to cim so3 cation excha ...201424631091
influenza vaccine effectiveness in spain 2013/14: subtype-specific early estimates using the cyceva study.adjusted early estimates of the 2013/14 influenza vaccine effectiveness (ve) in spain for all age groups was 35% (95% ci: -9 to 62), 33% (95% ci: -33 to 67) and 28% (95% ci: -33 to 61) against any influenza virus type, a(h1n1)pdm09 and a(h3n2) viruses, respectively. for the population targeted for vaccination, the adjusted ve was 44% (95% ci: -11 to 72), 36% (95% ci: -64 to 75) and 42% (95% ci: -29 to 74), respectively. these preliminary results in spain suggest a suboptimal protective effect of ...201424626206
mucosal immunization with a candidate universal influenza vaccine reduces virus transmission in a mouse model.pandemic influenza is a major public health concern, but conventional strain-matched vaccines are unavailable early in a pandemic. candidate "universal" vaccines targeting the viral antigens nucleoprotein (np) and matrix 2 (m2), which are conserved among all influenza a virus strains and subtypes, could be manufactured in advance for use at the onset of a pandemic. these vaccines do not prevent infection but can reduce disease severity, deaths, and virus titers in the respiratory tract. we hypot ...201424623430
detection of nonhemagglutinating influenza a(h3) viruses by enzyme-linked immunosorbent assay in quantitative influenza virus culture.to assess the efficacy of novel antiviral drugs against influenza virus in clinical trials, it is necessary to quantify infectious virus titers in respiratory tract samples from patients. typically, this is achieved by inoculating virus-susceptible cells with serial dilutions of clinical specimens and detecting the production of progeny virus by hemagglutination, since influenza viruses generally have the capacity to bind and agglutinate erythrocytes of various species through their hemagglutini ...201424622097
stability of neuraminidase in inactivated influenza vaccines.influenza vaccines are effective in protecting against illness and death caused by this seasonal pathogen. antibodies that block the function of either hemagglutinin (ha) or neuraminidase (na) contribute to vaccine efficacy, however vaccine potency is based only on ha content. na protein content in vaccines varies from season to season due to differences in the relative amounts of ha and na in influenza a, h1n1 and h3n2, and influenza b viruses that are selected for each manufacturing campaign. ...201424613525
preexisting cd4+ t-cell immunity in human population to avian influenza h7n9 virus: whole proteome-wide immunoinformatics analyses.in 2013, a novel avian influenza h7n9 virus was identified in human in china. the antigenically distinct h7n9 surface glycoproteins raised concerns about lack of cross-protective neutralizing antibodies. epitope-specific preexisting t-cell immunity was one of the protective mechanisms in pandemic 2009 h1n1 even in the absence of cross-protective antibodies. hence, the assessment of preexisting cd4+ t-cell immunity to conserved epitopes shared between h7n9 and human influenza a viruses (iav) is c ...201424609014
metal enhanced fluorescence on nanoporous gold leaf-based assay platform for virus detection.in the present study, a rapid, sensitive and quantitative detection of influenza a virus targeting hemagglutinin (ha) was developed using hybrid structure of quantum dots (qds) and nanoporous gold leaf (npgl). npgl film was prepared by dealloying bimetallic film where its surface morphology and roughness were fairly controlled. anti-influenza a virus ha antibody (ab66189) was bound with npgl and amine (-nh2) terminated qds. these biofunctionalized npgl and qds formed a complex with the influenza ...201424607620
impact of 2009 pandemic influenza among vietnamese children based on a population-based prospective surveillance from 2007 to 2011.influenza virus is one of the major viral pathogens causing pediatric acute respiratory infection (ari). the spread of pandemic influenza a (a(h1n1)pdm09) in 2009 around the globe had a huge impact on global health.201424602158
the host protease tmprss2 plays a major role in in vivo replication of emerging h7n9 and seasonal influenza viruses.proteolytic cleavage of the hemagglutinin (ha) protein is essential for influenza a virus (iav) to acquire infectivity. this process is mediated by a host cell protease(s) in vivo. the type ii transmembrane serine protease tmprss2 is expressed in the respiratory tract and is capable of activating a variety of respiratory viruses, including low-pathogenic (lp) iavs possessing a single arginine residue at the cleavage site. here we show that tmprss2 plays an essential role in the proteolytic activ ...201424600012
supplementation of influenza split vaccines with conserved m2 ectodomains overcomes strain specificity and provides long-term cross protection.current influenza vaccines do not provide good protection against antigenically different influenza a viruses. as an approach to overcome strain specificity of protection, this study demonstrates significantly improved long-term cross protection by supplementing split vaccines with a conserved molecular target, a repeat of the influenza m2 ectodomain (m2e) expressed on virus-like particles (m2e5x vlps) in a membrane-anchored form. intramuscular immunization with h1n1 split vaccine (a/california/ ...201424590045
1,2,3-triazole-containing derivatives of rupestonic acid: click-chemical synthesis and antiviral activities against influenza viruses.two series of rupestonic acid derivatives, (1-substituted-1h-1,2,3-triazol-4-yl)methyl 2-((5r,8s,8as)-3,8-dimethyl-2-oxo-1,2,4,5,6,7,8,8a-octahydroazulen-5-yl)acrylate and n-(1-substituted-1h-1,2,3-triazol-4-yl)methyl 2-((5r,8s,8as)-3,8-dimethyl-2-oxo-1,2,4,5,6,7,8,8a-octahydroazulen-5-yl)acrylamide were easily and efficiently synthesized via click chemistry. these compounds were tested for their in vitro activities against various strains of influenza a virus (h1n1, oseltamivir resistant h1n1, ...201424583605
oseltamivir-zanamivir combination therapy is not superior to zanamivir monotherapy in mice infected with influenza a(h3n2) and a(h1n1)pdm09 viruses.the efficacy of oseltamivir-zanamivir combination therapy compared to that of monotherapy was evaluated in mice infected with influenza a(h3n2) or a(h1n1)pdm09 viruses. for a(h3n2) virus, zanamivir monotherapy and oseltamivir-zanamivir combination showed significant reduction of mean weight loss compared to oseltamivir. zanamivir monotherapy also conferred decreased mortality, weight loss and lung viral titers (lvt) compared to oseltamivir for a(h1n1)pdm09 wild-type virus. intermediate benefits ...201424583158
synthesis and anti-influenza activities of novel baicalein analogs.a series of novel flavones derivatives were synthesized based on modification of the active ingredients of a traditional chinese medicine scutellaria baicalensis georgi and screened for anti-influenza activity. the synthetic baicalein (flavone) analogs, especially with the b-rings substituted with bromine atoms, were much more potent than oseltamivir or ribavirin against h1n1 tamiflu-resistant (h1n1 tr) virus and usually with more favorable selectivity. the most promising were 5b, 5c, 6b and 6c, ...201424572377
estimates of mortality attributable to influenza and rsv in the united states during 1997-2009 by influenza type or subtype, age, cause of death, and risk status.influenza and respiratory syncytial virus (rsv) cause substantial mortality from respiratory and other causes in the usa, especially among people aged 65 and older.201424975705
universal immunity to influenza must outwit immune evasion.although an influenza vaccine has been available for 70 years, influenza virus still causes seasonal epidemics and worldwide pandemics. currently available vaccines elicit strain-specific antibody (ab) responses to the surface haemagglutinin (ha) and neuraminidase (na) proteins, but these can be ineffective against serologically-distinct viral variants and novel subtypes. thus, there is a great need for cross-protective or "universal" influenza vaccines to overcome the necessity for annual immun ...201424971078
surveillance of influenza virus during 2010-2012 in changsha, china.the objective of this study was to examine the circulating influenza viruses in changsha, china, during 2010-2012. nasopharyngeal specimens were collected from persons with influenza-like illness (ili) who presented for care at two hospitals. of 2,955 patients tested, 278/(9.4%) were positive for influenza virus: 116/(41.7%) were influenza type a(h3n2), 79/(28.4%) were type a(h1n1) pandemic 2009 (pdm09) and 83/(29.9%) were influenza type b. the rates of virus detection varied by age and sex. the ...201424968671
higher vaccine effectiveness in seasons with predominant circulation of seasonal influenza a(h1n1) than in a(h3n2) seasons: test-negative case-control studies using surveillance data, spain, 2003-2011.we used data provided by the spanish influenza surveillance system to measure seasonal influenza vaccine effectiveness (ve) against medically attended cases, laboratory confirmed with the predominately circulating influenza virus over eight seasons (2003-2011).201424968153
introductions and evolution of human-origin seasonal influenza a viruses in multinational swine populations.the capacity of influenza a viruses to cross species barriers presents a continual threat to human and animal health. knowledge of the human-swine interface is particularly important for understanding how viruses with pandemic potential evolve in swine hosts. we sequenced the genomes of 141 influenza viruses collected from north american swine during 2002 to 2011 and identified a swine virus that possessed all eight genome segments of human seasonal a/h3n2 virus origin. a molecular clock analysi ...201424965467
serological report of pandemic and seasonal human influenza virus infection in dogs in southern china.from january to july 2012, we looked for evidence of subclinical a (h1n1) pdm09 and seasonal human influenza viruses infections in healthy dogs in china. sera from a total of 1920 dogs were collected from guangdong, guangxi, fujian and jiangxi provinces. we also examined archived sera from 66 dogs and cats that were collected during 2008 from these provinces. using hemagglutination inhibition (hi) and microneutralization (mn) assays, we found that only the dogs sampled in 2012 had elevated antib ...201424965232
epidemiology of influenza virus types and subtypes in south africa, 2009-2012.to determine clinical and epidemiologic differences between influenza caused by different virus types and subtypes, we identified patients and tested specimens. patients were children and adults hospitalized with confirmed influenza and severe acute respiratory illness (sari) identified through active, prospective, hospital-based surveillance from 2009-2012 in south africa. respiratory specimens were tested, typed, and subtyped for influenza virus by pcr. of 16,005 sari patients tested, 1,239 (8 ...201424960314
characterization of drug-resistant influenza virus a(h1n1) and a(h3n2) variants selected in vitro with laninamivir.neuraminidase inhibitors (nais) play a major role for managing influenza virus infections. the widespread oseltamivir resistance among 2007-2008 seasonal a(h1n1) viruses and community outbreaks of oseltamivir-resistant a(h1n1)pdm09 strains highlights the need for additional anti-influenza virus agents. laninamivir is a novel long-lasting nai that has demonstrated in vitro activity against influenza a and b viruses, and its prodrug (laninamivir octanoate) is in phase ii clinical trials in the uni ...201424957832
conservation of t cell epitopes between seasonal influenza viruses and the novel influenza a h7n9 virus.a novel avian influenza a (h7n9) virus recently emerged in the yangtze river delta and caused diseases, often severe, in over 130 people. this h7n9 virus appeared to infect humans with greater ease than previous avian influenza virus subtypes such as h5n1 and h9n2. while there are other potential explanations for this large number of human infections with an avian influenza virus, we investigated whether a lack of conserved t-cell epitopes between endemic h1n1 and h3n2 influenza viruses and the ...201424950786
a packaged paper fluidic-based microdevice for detecting gene expression of influenza a virus.pathotyping and subtyping of influenza a virus were performed with a packaged paper fluidic-based analytical microdevice (pfam) after one-step reverse transcription-polymerase chain reaction (rt-pcr). the pfam contains two test lines: one for detecting m gene to identify the influenza a virus and another for haemagglutinin subtyping to determine the viral strain among h1n1, h3n2, and h5n1. the m gene and the haemagglutinin gene (h1, h3, and h5 genes) were amplified by using the digoxigenin and t ...201424949821
serological and molecular prevalence of swine influenza virus on farms in northwestern mexico.the aim of this study was to provide an overview of the epidemiological status of swine influenza viruses in pigs from northwestern mexico in 2008-2009. a serological and molecular survey was conducted in 150 pigs from 15 commercial farms in sonora, mexico (northwestern region of mexico). the serological data showed that 55% of the sera were positive for the h1n1 subtype, 59% for the h3n2 subtype, and 38% for both subtypes. overall, 16.6% (25/150) of the samples were positive for type a influenz ...201424925324
molecular epidemiology and evolution of a(h1n1)pdm09 and h3n2 virus during winter 2012-2013 in beijing, china.in order to evaluate the epidemiology of influenza a and its surface antigens (haemagglutinin [ha] and neuraminidase [na]) for molecular epidemiology and evolution analysis during winter 2012-2013 in beijing, china, we worked within the framework of the chinese national influenza center and collected nasal swabs of patients presenting with influenza-like illness. we found that both a(h1n1)pdm09 (46.8%) and h3n2 (53.2%) viruses were the predominant strains during the 2012-2013 influenza epidemic. ...201424911284
a brief introduction to influenza a virus in swine.influenza a viruses (iav) of the orthomyxoviridae virus family cause one of the most important respiratory diseases in pigs as well as humans. repeated outbreaks and rapid spread of genetically and antigenically distinct iavs represent a considerable challenge for animal production and public health. this overlap between human and animal health is a prime example of the "one health" concept. although only subtypes of h1n1, h1n2, and h3n2 are endemic in swine around the world, considerable divers ...201424899434
influenza virus h1n1 inhibition by serine protease inhibitor (serpin) antithrombin iii.endogenous serine protease inhibitors (serpins) are anti-inflammatory mediators with multiple biologic functions. serpins are also part of the early innate immune response to viral infection that includes mannose binding lectins, soluble cd14, defensins and antimicrobial peptides. recently, serpin antithrombin iii (atiii) was shown to have broad-spectrum antiviral activity against hiv, hsv and hcv. we tested atiii's antiviral activity against a variety of influenza virus strains. in our studies ...201424883334
detection of avian influenza a/h7n9/2013 virus by real-time reverse transcription-polymerase chain reaction.the first case of avian influenza a/h7n9 infection was reported in shanghai in mid-february, 2013; by may 1, 2013, it had infected 127 people and caused 26 deaths in 10 provinces in china. therefore, it is important to obtain reliable epidemiological data on the spread of this new infectious agent, a need that may be best met by the development of novel molecular methods. here, a new method was described for the detection of avian influenza a/h7n9 using real-time reverse transcription-polymerase ...201424880072
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