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oseltamivir population pharmacokinetics in the ferret: model application for pharmacokinetic/pharmacodynamic study design.the ferret is a suitable small animal model for preclinical evaluation of efficacy of antiviral drugs against various influenza strains, including highly pathogenic h5n1 viruses. rigorous pharmacokinetics/pharmacodynamics (pk/pd) assessment of ferret data has not been conducted, perhaps due to insufficient information on oseltamivir pk. here, based on pk data from several studies on both uninfected and influenza-infected groups (i.e., with influenza a viruses of h5n1 and h3n2 subtypes and an inf ...201526460484
influenza virus reassortment is enhanced by semi-infectious particles but can be suppressed by defective interfering particles.a high particle to infectivity ratio is a feature common to many rna viruses, with ~90-99% of particles unable to initiate a productive infection under low multiplicity conditions. a recent publication by brooke et al. revealed that, for influenza a virus (iav), a proportion of these seemingly non-infectious particles are in fact semi-infectious. semi-infectious (si) particles deliver an incomplete set of viral genes to the cell, and therefore cannot support a full cycle of replication unless co ...201526440404
addition of n-glycosylation sites on the globular head of the h5 hemagglutinin induces the escape of highly pathogenic avian influenza a h5n1 viruses from vaccine-induced immunity.highly pathogenic avian influenza a h5n1 viruses remain endemic in poultry in several countries and still constitute a pandemic threat. since the early 20th century, we experienced four influenza a pandemics. h3n2 and h1n1pdm09 viruses that respectively emerged during 1968 and 2009 pandemics are still responsible for seasonal epidemics. these viruses evolve regularly by substitutions in antigenic sites of the hemagglutinin (ha), which prevent neutralization by antibodies directed against previou ...201526433051
interim estimates of divergence date and vaccine strain match of human influenza a(h3n2) virus from systematic influenza surveillance (2010-2015) in hangzhou, southeast of china.in the post-pandemic period 2010-2015, seasonal influenza a(h3n2) virus predominated in hangzhou, southeast of china, with an increased activity and semi-annual seasons. this study utilized ha virus gene segment sequences to analyze the divergence date and vaccine strain match of human influenza a(h3n2) virus from systematic influenza surveillance in hangzhou.201526417878
influenza virus survival in aerosols and estimates of viable virus loss resulting from aerosolization and air-sampling.using a collison nebulizer, aerosols of influenza (a/udorn/307/72 h3n2) were generated within a controlled experimental chamber, from known starting virus concentrations. air samples collected after variable suspension times were tested quantitatively using both plaque and polymerase chain reaction assays, to compare the proportion of viable virus against the amount of detectable viral rna. these experiments showed that whereas influenza rna copies were well preserved, the number of viable virus ...201526412395
new functionally-enhanced soy proteins as food ingredients with anti-viral activity.respiratory viruses are a major public health problem because of their prevalence and high morbidity rate leading to considerable social and economic implications. cranberry has therapeutic potential attributed to a comprehensive list of phytochemicals including anthocyanins, flavonols, and unique a-type proanthocyanidins. soy flavonoids, including isoflavones, have demonstrated anti-viral effects in vitro and in vivo. recently, it was demonstrated that edible proteins can efficiently sorb and c ...201526396978
role of substitutions in the hemagglutinin in the emergence of the 1968 pandemic influenza virus.hemagglutinin (ha) of h3n2/1968 pandemic influenza viruses differs from the putative avian precursor by seven amino acid substitutions. substitutions q226l and g228s are known to be essential for adaptation of avian ha to mammals. we found that introduction of avian-virus-like amino acids at five other ha positions (positions 62, 81, 92, 144, and 193) of a/hong kong/1/1968 virus decreased viral replication in human cells and transmission in pigs. thus, substitutions at some of these positions fa ...201526378170
rig-i signaling is essential for influenza b virus-induced rapid interferon gene expression.influenza b virus causes annual epidemics and, along with influenza a virus, accounts for substantial disease and economic burden throughout the world. influenza b virus infects only humans and some marine mammals and is not responsible for pandemics, possibly due to a very low frequency of reassortment and a lower evolutionary rate than that of influenza a virus. influenza b virus has been less studied than influenza a virus, and thus, a comparison of influenza a and b virus infection mechanism ...201526378160
in vitro validation of self designed "universal human influenza a sirna".the genomic variability of influenza a virus (iav) makes it difficult for the existing vaccines or anti-influenza drugs to control. the sirna targeting viral gene induces rnai mechanism in the host and silent the gene by cleaving mrna. in this study, we developed an universal sirna and validated its efficiency in vitro. the sirna was designed rationally, targeting the most conserved region (delineated with the help of multiple sequence alignment) of m gene of iav strains. three level screening m ...201526349314
[analysis of the mechanism of a three-wave epidemic influenza a virus cvcle].a three-wave epidemic cycle caused by a new serotype agent is simulated. the mechanism of stepwise recession in a stratum of the susceptible persons is examined. a group of asymptomatic infected individuals as well as an antigen activity index, which regulates the intensity of input streams into the groups of infected patients, are introduced into the model. morbidity rate is additionally regulated by the virulence. the model is identified according to the observations of the three-wave passage ...201526349219
sex differences in h7n9 influenza a virus pathogenesis.sex, gender and age have an impact on incidence and severity of several infectious diseases. here, we analyzed reported human cases of avian h7n9 influenza a virus infections for potential sex-dependent incidence and mortality. we report that females in their reproductive years display an increased tendency to die of h7n9 influenza than males (female-to-male ratio=1.2). next, we challenged this potential sex-dependent difference in influenza disease outcome using a mouse infection model. in gene ...201526319064
cross-species infectivity of h3n8 influenza virus in an experimental infection in swine.avian influenza a viruses have gained increasing attention due to their ability to cross the species barrier and cause severe disease in humans and other mammal species as pigs. h3 and particularly h3n8 viruses, are highly adaptive since they are found in multiple avian and mammal hosts. h3n8 viruses have not been isolated yet from humans; however, a recent report showed that equine influenza a viruses (iavs) can be isolated from pigs, although an established infection has not been observed thus ...201526311894
[susceptibility of human influenza a (h3n2) viruses to neuraminidase inhibitors isolated during 2011-2012 in china].to analyze the susceptibility of influenza a (h3n2) viruses to neuraminidase inhibitors during 2011-2012 in mainland china.201526310330
age-related prevalence of cross-reactive antibodies against influenza a(h3n2) variant virus, germany, 2003 to 2010.to estimate susceptibility to the swine-origin influenza a(h3n2) variant virus (a(h3n2)v) in the german population, we investigated cross-reactive antibodies against this virus and factors associated with seroprotective titre using sera from representative health examination surveys of children and adolescents (n = 815, 2003–06) and adults (n = 600, 2008–10). antibodies were assessed by haemagglutination inhibition assay (hi); in our study an hi titre ≥ 40 was defined as seroprotective. we inves ...201526290488
detection of influenza a(h3n2) virus in children with suspected mumps during winter 2014/15 in england.influenza a(h3n2) virus was detected in oral fluid from 16/107 children (aged 2 to 12 years) with a clinical diagnosis of mumps, who were sampled between december 2014 and february 2015 in england, during the peak of the 2014/15 influenza season. sequence analysis of an a(h3n2) virus from a child with suspected mumps showed the virus was similar to other circulating a(h3n2) viruses detected in winter 2014/15, which were antigenically drifted from the a(h3n2) vaccine strain.201526290428
a broadly neutralizing human monoclonal antibody is effective against h7n9.emerging strains of influenza represent a significant public health threat with potential pandemic consequences. of particular concern are the recently emerged h7n9 strains which cause pneumonia with acute respiratory distress syndrome. estimates are that nearly 80% of hospitalized patients with h7n9 have received intensive care unit support. vis410, a human antibody, targets a unique conserved epitope on influenza a. we evaluated the efficacy of vis410 for neutralization of group 2 influenza st ...201526283346
immunogenicity and safety of an inactivated quadrivalent influenza vaccine in healthy adults: a phase ii, open-label, uncontrolled trial in japan.two antigenically distinct b strain lineages of influenza virus have co-circulated since the mid-1980s; however, inactivated trivalent influenza vaccines contain only one b lineage. the mismatch between the circulating and vaccine lineages has been a worldwide issue. in this study, an inactivated quadrivalent influenza vaccine (qiv) candidate containing two b lineages was manufactured and its immunogenicity and safety evaluated in an open-label, uncontrolled trial. in this phase ii trial, 50 sub ...201526272602
human mir-3145 inhibits influenza a viruses replication by targeting and silencing viral pb1 gene.micrornas (mirnas) play an important role in the regulation of gene expression and are involved in many cellular processes including inhibition of viral replication in infected cells. in this study, three subtypes of influenza a viruses (ph1n1, h5n1 and h3n2) were analyzed to identify candidate human mirnas targeting and silencing viral genes expression. candidate human mirnas were predicted by mirbase and rnahybrid based on minimum free energy (mfe) and hybridization patterns between human mirn ...201526080461
swine influenza a(h3n2) virus infection in immunocompromised man, italy, 2014.because swine influenza virus infection is seldom diagnosed in humans, its frequency might be underestimated. we report a immunocompromised hematologic patient with swine influenza a(h3n2) virus in 2014 in italy. local pigs were the source of this human infection.201526079745
quantitative analysis of influenza a (h3n2) e119v and r292k variants in clinical specimens by real-time reverse transcription polymerase chain reaction.because influenza virus isolates after cell culture are required to determine their susceptibility to neuraminidase inhibitors, the differences in normal or low-susceptibility variant population frequencies between clinical samples and isolates have not been considered.201526071346
abnormal expressions of inflammatory-related mediators and inhibition of fat metabolism in mice infected with influenza a virus.the pathophysiological role of influenza infection is poorly understood. in this study, one non-neurovirulent virus (iav/aichi/2/68/h3n2) strain was used to infect intra-nasally mice at different age to investigate the mechanism of cerebral edema formation and lower activities of mitochondria enzymes after influenza a virus (iav) infection. mice suffered 46.4% mortality in newborn compared with 96.0% in weanling, 100% in adult on day 7, respectively. iav-rna was easily detected in the brain of n ...201526051732
influenza a virus coinfection through transmission can support high levels of reassortment.the reassortment of gene segments between influenza viruses increases genomic diversity and plays an important role in viral evolution. we have shown previously that this process is highly efficient within a coinfected cell and, given synchronous coinfection at moderate or high doses, can give rise to ~60 to 70% of progeny shed from an animal host. conversely, reassortment in vivo can be rendered undetectable by lowering viral doses or extending the time between infections. one might also predic ...201526041285
the effects of h3n2 swine influenza virus infection on tlrs and rlrs signaling pathways in porcine alveolar macrophages.swine influenza is an economically important respiratory disease of swine resulting from infection with influenza a virus. swine influenza virus (siv) becomes the focus as pigs have been hypothesized to serve as an intermediate host for the adaptation of avian influenza viruses to humans or as mixing vessels for the generation of genetically reassortant viruses. the ability of the innate immune system to detect and respond to pathogens is important for survival. therefore, there is a critical ne ...201526021751
[virological characteristics of influenza a (h3n2) virus in mainland china during 2013-2014].to analyze the antigenic and genetic characteristics of the influenza a (h3n2) virus in mainland china during the surveillance year of 2013-2014, the antigenic characteristics of h3n2 virus were analyzed using reference ferret anti-sera. the nucleotide sequences of the viruses were determined by sanger dideoxy sequencing, phylogenetic trees were constructed with the neighbor-joining method, and the genetic characteristics of the viruses were determined in comparison to current vaccine strains. t ...201525997327
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
effective lethal mutagenesis of influenza virus by three nucleoside analogs.lethal mutagenesis is a broad-spectrum antiviral strategy that exploits the high mutation rate and low mutational tolerance of many rna viruses. this approach uses mutagenic drugs to increase viral mutation rates and burden viral populations with mutations that reduce the number of infectious progeny. we investigated the effectiveness of lethal mutagenesis as a strategy against influenza virus using three nucleoside analogs, ribavirin, 5-azacytidine, and 5-fluorouracil. all three drugs were acti ...201525589650
viral etiology of community-acquired pneumonia among adolescents and adults with mild or moderate severity and its relation to age and severity.better knowledge of distribution of respiratory viruses (rvs) in adolescents and adults with community-acquired pneumonia (cap) is needed.201525812108
protection against multiple influenza a virus strains induced by candidate recombinant vaccine based on heterologous m2e peptides linked to flagellin.matrix 2 protein ectodomain (m2e) is considered a promising candidate for a broadly protective influenza vaccine. m2e-based vaccines against human influenza a provide only partial protection against avian influenza viruses because of differences in the m2e sequences. in this work, we evaluated the possibility of obtaining equal protection and immune response by using recombinant protein on the basis of flagellin as a carrier of the m2e peptides of human and avian influenza a viruses. recombinant ...201525799221
diversity in compartmental dynamics of gene regulatory networks: the immune response in primary influenza a infection in mice.current approaches to study transcriptional profiles post influenza infection typically rely on tissue sampling from one or two sites at a few time points, such as spleen and lung in murine models. in this study, we infected female c57/bl6 mice intranasally with mouse-adapted h3n2/hong kong/x31 avian influenza a virus, and then analyzed the gene expression profiles in four different compartments (blood, lung, mediastinal lymph nodes, and spleen) over 11 consecutive days post infection. these dat ...201526413862
antiviral activities of several oral traditional chinese medicines against influenza viruses.influenza is still a serious threat to human health with significant morbidity and mortality. the emergence of drug-resistant influenza viruses poses a great challenge to existing antiviral drugs. traditional chinese medicines (tcms) may be an alternative to overcome the challenge. here, 10 oral proprietary chinese medicines were selected to evaluate their anti-influenza activities. these drugs exhibit potent inhibitory effects against influenza a h1n1, influenza a h3n2, and influenza b virus. i ...201526557857
anti-viral and cytotoxic norbisabolane sesquiterpenoid glycosides from phyllanthus emblica and their absolute configurations.in an effort to identify anti-viral and cytotoxic compounds from phyllanthus spp., 14 highly oxygenated norbisabolane sesquiterpenoids, phyllaemblicins h1-h14, were isolated from the roots of phyllanthus emblica linn, along with phyllaemblicins b and c and glochicoccinoside d. their structures were determined on the basis of detailed spectroscopic analysis and chemical methods. determination of absolute configurations of these compounds was facilitated by theoretical calculations of electronic c ...201526074492
hemagglutinin sequence conservation guided stem immunogen design from influenza a h3 subtype.seasonal epidemics caused by influenza a (h1 and h3 subtypes) and b viruses are a major global health threat. the traditional, trivalent influenza vaccines have limited efficacy because of rapid antigenic evolution of the circulating viruses. this antigenic variability mediates viral escape from the host immune responses, necessitating annual vaccine updates. influenza vaccines elicit a protective antibody response, primarily targeting the viral surface glycoprotein hemagglutinin (ha). however, ...201526167164
preparation of monopegylated cyanovirin-n's derivative and its anti-influenza a virus bioactivity in vitro and in vivo.influenza a virus (iav) has been raising public health and safety concerns worldwide. cyanovirin-n (cvn) is a prominent anti-iav candidate, but both cytotoxicity and immunogenicity have hindered the development of this protein as a viable therapy. in this article, linker-cvn (lcvn) with a flexible and hydrophilic polypeptide at the n-terminus was efficiently produced from the cytoplasm of escherichia coli at a >15-l scale. pegylation at the n-terminal α-amine of lcvn was also reformed as 20 kda ...201525713409
a nonfusogenic antigen mimic of influenza hemagglutinin glycoproteins constituted with soluble full-length ha1 and truncated ha2 proteins expressed in e. coli.a novel method is proposed to produce a soluble recombinant antigen mimic, constituted with full-length ha1 and truncated ha2 individually expressed in e. coli, instead of a precursor form of hemagglutinin protein, that is similar to the naturally processed and disulfide-linked ha1/ha2 on the envelope of the influenza a virus strain x-31 (h3n2). a truncated ectodomain of ha2 subunit, ha2(23-185)/c137s, lacked two membrane-interacting sequences, i.e., the n-terminal fusion peptide as well as the ...201525288022
mouse lung slices: an ex vivo model for the evaluation of antiviral and anti-inflammatory agents against influenza viruses.the influenza a virus is notoriously known for its ability to cause recurrent epidemics and global pandemics. antiviral therapy is effective when treatment is initiated within 48h of symptom onset, and delaying treatment beyond this time frame is associated with decreased efficacy. research on anti-inflammatory therapy to ameliorate influenza-induced inflammation is currently underway and seems important to the impact on the clinical outcome. both antiviral and anti-inflammatory drugs with novel ...201526022197
serological evidence and risk factors for swine influenza infections among chinese swine workers in guangdong province.during july to september 2014, we performed a controlled, cross-sectional, seroepidemiologic study among 203 swine workers and 115 control subjects in guangdong province. sera were tested using a hemagglutination inhibition assay against locally-isolated swine h3n2 and h1n1 viruses and commercially-obtained human influenza viral antigens. we found swine workers had a greater prevalence and odds of seropositivity against the swine h3n2 virus (17.3% vs. 7.0%; adjusted or, 3.4; 95% ci, 1.1 -10.7). ...201526016740
[monitoring of influenza and other respiratory diseases causative agents in children, hospitalized with community-acquired pneumonia in 2012-2013 epidemic season].study the circulation of respiratory viruses in children with community-acquired pneumonia (cap) during the period from october 2012 to may 2013.201526016346
microneedle patch delivery to the skin of virus-like particles containing heterologous m2e extracellular domains of influenza virus induces broad heterosubtypic cross-protection.a broadly cross-protective influenza vaccine that can be administrated by a painless self-immunization method would be a value as a potential universal mass vaccination strategy. this study developed a minimally-invasive microneedle (mn) patch for skin vaccination with virus-like particles containing influenza virus heterologous m2 extracellular (m2e) domains (m2e5x vlps) as a universal vaccine candidate without adjuvants. the stability of m2e5x vlp-coated microneedles was maintained for 8weeks ...201526003039
egg-adaptive mutations in h3n2v vaccine virus enhance egg-based production without loss of antigenicity or immunogenicity.the recently detected zoonotic h3n2 variant influenza a (h3n2v) viruses have caused 343 documented cases of human infection linked to contact with swine. an effective vaccine is needed for these viruses, which may acquire transmissibility among humans. however, viruses isolated from human cases do not replicate well in embryonated chicken eggs, posing an obstacle to egg-based vaccine production. to address this issue, we sought to identify egg-adaptive mutations in surface proteins that increase ...201525999284
humoral and cellular immune responses after influenza vaccination in patients with postcancer fatigue.the aim of this study was to compare humoral and cellular immune responses to influenza vaccination in cancer survivors with and without severe symptoms of fatigue. severely fatigued (n = 15) and non-fatigued (n = 12) disease-free cancer survivors were vaccinated against seasonal influenza. humoral immunity was evaluated at baseline and post-vaccination by a hemagglutination inhibition assay. cellular immunity was evaluated at baseline and post-vaccination by lymphocyte proliferation and activat ...201525996472
influenza vaccine effectiveness in preventing inpatient and outpatient cases in a season dominated by vaccine-matched influenza b virus.studies that have evaluated the influenza vaccine effectiveness (ve) to prevent laboratory-confirmed influenza b cases are uncommon, and few have analyzed the effect in preventing hospitalized cases. we have evaluated the influenza ve in preventing outpatient and hospitalized cases with laboratory-confirmed influenza in the 2012-2013 season, which was dominated by a vaccine-matched influenza b virus. in the population covered by the navarra health service, all hospitalized patients with influenz ...201525996366
haemagglutinin mutations and glycosylation changes shaped the 2012/13 influenza a(h3n2) epidemic, houston, texas.while the early start and higher intensity of the 2012/13 influenza a virus (iav) epidemic was not unprecedented, it was the first iav epidemic season since the 2009 h1n1 influenza pandemic where the h3n2 subtype predominated. we directly sequenced the genomes of 154 h3n2 clinical specimens collected throughout the epidemic to better understand the evolution of h3n2 strains and to inform the h3n2 vaccine selection process. phylogenetic analyses indicated that multiple co-circulating clades and c ...201525990233
age-specific epidemic waves of influenza and respiratory syncytial virus in a subtropical city.both influenza and respiratory syncytial virus (rsv) are active throughout the year in subtropical or tropical regions, but few studies have reported on age-specific seasonal patterns of these viruses. we examined the age-specific epidemic curves of laboratory-confirmed cases of influenza a (subtyped into seasonal a(h1n1), a(h3n2), and pandemic virus a(h1n1)pdm09), influenza b and respiratory syncytial virus (rsv), in subtropical city hong kong from 2004 to 2013. we found that different types an ...201525981824
computational identification of antigenicity-associated sites in the hemagglutinin protein of a/h1n1 seasonal influenza virus.the antigenic variability of influenza viruses has always made influenza vaccine development challenging. the punctuated nature of antigenic drift of influenza virus suggests that a relatively small number of genetic changes or combinations of genetic changes may drive changes in antigenic phenotype. the present study aimed to identify antigenicity-associated sites in the hemagglutinin protein of a/h1n1 seasonal influenza virus using computational approaches. random forest regression (rfr) and s ...201525978416
[estimation of hospitalization rate of laboratory confirmed influenza cases in jingzhou city, hubei province, 2010-2012].to estimate the hospitalization rate of severe acute respiratory infection (sari) cases attributable to influenza in jingzhou city, hubei province from 2010 to 2012.201525975397
genetic variation in the hemagglutinin of a(h1n1) 09pdm and a(h3n2) influenza viruses in the beijing area from 2009 to 2014.a(h1n1) 09pdm and a(h3n2) influenza viruses are the main cause of occasional influenza pandemics and seasonal influenza epidemics around the world. unfortunately, the understanding of long-term genetic variation in these viruses remains limited.201525974995
etiological role of ortho- and paramyxoviruses in acute respiratory tract infections among children aged < 4 years in bulgaria.influenza viruses (family orthomyxoviridae); respiratory-syncytial virus (rsv), human metapneumovirus (hmpv), and parainfluenza viruses (hpiv) type 1, 2 and 3 (family paramyxoviridae) are among the most common causes of acute respiratory tract infections (arti) in infants and young children. the aim of this study was to determine the contribution of these viruses in cases of arti requiring medical attention among children aged < 4 years during the 2012/13 and 2013/14 winter seasons in bulgaria.201525974986
sesquiterpenes from the roots of illicium oligandrum.two new sesquiterpenes, oligandrin (1) and oligandric acid (2), together with three analogues, tashironin a (3), tashironin (4), and oplodiol (5), were isolated from the roots of illicium oligandrum. the structures of new compounds were determined based on 1d and 2d nmr experiments and x-ray diffraction. compound 1 represents a presumed biosynthetic precursor of seco-prezizaane sesquiterpenes which consists of a novel 6/6/5 tricarbocyclic skeleton. compound 2 is the first example of chamipinene- ...201525966312
cross-reactive neuraminidase-inhibiting antibodies elicited by immunization with recombinant neuraminidase proteins of h5n1 and pandemic h1n1 influenza a viruses.neuraminidase (na), an influenza virus envelope glycoprotein, removes sialic acid from receptors for virus release from infected cells. for this study, we used a baculovirus-insect cell expression system to construct and purify recombinant na (rna) proteins of h5n1 (a/vietnam/1203/2004) and pandemic h1n1 (ph1n1) (a/texas/05/2009) influenza viruses. balb/c mice immunized with these proteins had high titers of na-specific igg and na-inhibiting (ni) antibodies against h5n1, ph1n1, h3n2, and h7n9 vi ...201525948745
interval between infections and viral hierarchy are determinants of viral interference following influenza virus infection in a ferret model.epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. this viral interference appears to be independent of any antigenic similarities between the viruses. we used the ferret model of human influenza to systematically investigate viral interference.201525943206
characterization of a novel oil-in-water emulsion adjuvant for swine influenza virus and mycoplasma hyopneumoniae vaccines.vaccines consisting of subunit or inactivated bacteria/virus and potent adjuvants are widely used to control and prevent infectious diseases. because inactivated and subunit antigens are often less antigenic than live microbes, a growing need exists for the development of new and improved vaccine adjuvants that can elicit rapid and long-lasting immunity. here we describe the development and characterization of a novel oil-in-water emulsion, ow-14. ow-14 contains low-cost plant-based emulsifiers ...201525936722
impact of the 2009 h1n1 pandemic on age-specific epidemic curves of other respiratory viruses: a comparison of pre-pandemic, pandemic and post-pandemic periods in a subtropical city.the 2009 h1n1 influenza pandemic caused offseason peaks in temperate regions but coincided with the summer epidemic of seasonal influenza and other common respiratory viruses in subtropical hong kong. this study was aimed to investigate the impact of the pandemic on age-specific epidemic curves of other respiratory viruses.201525928217
dynamic virus-bacterium interactions in a porcine precision-cut lung slice coinfection model: swine influenza virus paves the way for streptococcus suis infection in a two-step process.swine influenza virus (siv) and streptococcus suis are common pathogens of the respiratory tract in pigs, with both being associated with pneumonia. the interactions of both pathogens and their contribution to copathogenesis are only poorly understood. in the present study, we established a porcine precision-cut lung slice (pcls) coinfection model and analyzed the effects of a primary siv infection on secondary infection by s. suis at different time points. we found that siv promoted adherence, ...201525916988
antiviral activity of the human cathelicidin, ll-37, and derived peptides on seasonal and pandemic influenza a viruses.human ll-37, a cationic antimicrobial peptide, was recently shown to have antiviral activity against influenza a virus (iav) strains in vitro and in vivo. in this study we compared the anti-influenza activity of ll-37 with that of several fragments derived from ll-37. we first tested the peptides against a seasonal h3n2 strain and the mouse adapted h1n1 strain, pr-8. the n-terminal fragment, ll-23, had slight neutralizing activity against these strains. in ll-23v9 serine 9 is substituted by vali ...201525909853
incidence of circulating antibodies against hemagglutinin of influenza viruses in the epidemic season 2013/2014 in poland.the aim of this study was to determine the level of antibodies against hemagglutinin of influenza viruses in the sera of people in different age groups in the epidemic season 2013/2014 in poland. the level of anti-hemagglutinin antibodies was determined by hemagglutination inhibition test (hai). a total number of 1,050 randomly selected sera was tested in seven age groups. the level of antibodies against influenza viruses was very low, which indicates that the people have not been vaccinated aga ...201525904002
influenza b virus-specific cd8+ t-lymphocytes strongly cross-react with viruses of the opposing influenza b lineage.influenza b viruses fall in two antigenically distinct lineages (b/victoria/2/1987 and b/yamagata/16/1988 lineage) that co-circulate with influenza a viruses of the h3n2 and h1n1 subtypes during seasonal epidemics. infections with influenza b viruses contribute considerably to morbidity and mortality in the human population. influenza b virus neutralizing antibodies, elicited by natural infections or vaccination, poorly cross-react with viruses of the opposing influenza b lineage. therefore, the ...201525900135
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