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incidence and clinical course of respiratory viral coinfections in children aged 0-59 months.clinical data available on coinfections are contradictory concerning both the number of viruses involved and the severity of the condition. a total of 114 patients aged 0-59 months with symptoms of respiratory tract infection were enrolled into the study. nasal and pharyngeal swabs were tested using the pcr method for the following 12 viruses: influenza a, influenza b, respiratory syncytial virus a (rsv a), respiratory syncytial virus b (rsv b), adenovirus, metapneumovirus, coronavirus 229e/nl63 ...201626801151
antibiotic prescription practices among children with influenza.the important factor in the development of resistance to antibiotics is their overuse, especially for viral respiratory infections. the aim of the study was to find out the frequency of the antibiotic therapy administrated to children with influenza. a total of 114 children younger than 59 months seeking care for the acute respiratory tract infection was enrolled into the study. the patients had influenza-like symptoms: fever > 38 °c, cough, and sore throat of less than 4 days duration. nasal an ...201626801146
the semi-synthesis of novel andrographolide analogues and anti-influenza virus activity evaluation of their derivatives.two novel andrographolide analogues with the structural motif of δ(8,17)-alkene exo-to-endo isomerization, ai78 and ai89, were semi-synthesized firstly. two series of derivatives were designed and synthesized based on the synthetic pathway (including series i: olefin isomerizing to endocyclic δ(8,9) and series ii: olefin isomerizing to endocyclic δ(7,8)). the anti-influenza virus activity in vitro for all derivatives was evaluated. among the compounds synthesized, compound 38 with benzyl amino g ...201626791013
ultrasensitive detection of influenza viruses with a glycan-based impedimetric biosensor.an ultrasensitive impedimetric glycan-based biosensor for reliable and selective detection of inactivated, but intact influenza viruses h3n2 was developed. such glycan-based approach has a distinct advantage over antibody-based detection of influenza viruses since glycans are natural viral receptors with a possibility to selectively distinguish between potentially pathogenic influenza subtypes by the glycan-based biosensors. build-up of the biosensor was carefully optimized with atomic force mic ...201626765527
correlates of protection against influenza in the elderly: results from an influenza vaccine efficacy trial.although a number of studies have investigated and quantified immune correlates of protection against influenza in adults and children, data on immune protection in the elderly are sparse. a recent vaccine efficacy trial comparing standard-dose with high-dose inactivated influenza vaccine in persons 65 years of age and older provided the opportunity to examine the relationship between values of three immunologic assays and protection against community-acquired a/h3n2 influenza illness. the high- ...201626762363
isolation of a novel h3n2 influenza virus containing a gene of h9n2 avian influenza in a dog in south korea in 2015.we isolated a serotype h3n2 influenza virus from a dog with severe respiratory distress in an animal clinic in south korea in 2015 and characterized the sequences of its eight genes. the following seven genes were derived from canine influenza virus: pb2, pb1, ha, np, na, m, and ns. however, the pa gene was derived from avian h9n2 influenza virus that is circulating in poultry in korea. these findings suggest that the continued surveillance of the influenza virus in dogs is warranted because hum ...201626757941
targeting host calpain proteases decreases influenza a virus infection.influenza a viruses (iav) trigger contagious acute respiratory diseases. a better understanding of the molecular mechanisms of iav pathogenesis and host immune responses is required for the development of more efficient treatments of severe influenza. calpains are intracellular proteases that participate in diverse cellular responses, including inflammation. here, we used in vitro and in vivo approaches to investigate the role of calpain signaling in iav pathogenesis. calpain expression and acti ...201626747784
multiplex rt-pcr detection of h3n2 influenza a virus in dogs.a multiplex rt-pcr (mrt-pcr) assay to detect h3n2 civ genomic segments was developed as a rapid and cost-effective method. its performance was evaluated with forty-six influenza a viruses from different hosts using three primer sets which amplify four segments of h3n2 civ simultaneously. the mrt-pcr has been successful in detecting the viral segments, indicating that it can improve the speed of diagnosis for h3n2 civ and its reassortants.201626738688
deep sequencing of influenza a virus from a human challenge study reveals a selective bottleneck and only limited intrahost genetic diversification.knowledge of influenza virus evolution at the point of transmission and at the intrahost level remains limited, particularly for human hosts. here, we analyze a unique viral data set of next-generation sequencing (ngs) samples generated from a human influenza challenge study wherein 17 healthy subjects were inoculated with cell- and egg-passaged virus. nasal wash samples collected from 7 of these subjects were successfully deep sequenced. from these, we characterized changes in the subjects' vir ...201627707932
oseltamivir resistance in an influenza a (h3n2) virus isolated from an immunocompromised patient during the 2014-2015 influenza season in alberta, canada.this manuscript describes the identification of an oseltamivir-resistant influenza a (h3n2) virus in a respiratory specimen collected from an immunocompromised patient in alberta, canada, during the 2014-2015 influenza season. following treatment with oseltamivir, neuraminidase (na) gene sequencing indicated the presence of an r292k mutation. phenotypic susceptibility testing by the na-star assay indicated a highly reduced inhibition by oseltamivir and normal inhibition by zanamivir. the use of ...201627442795
seroepidemiological evidence of subtype h3n8 influenza virus infection among pet dogs in china.the h3n8 virus and the h3n2 virus are the main subtypes of canine influenza virus (civ). h3n8 civ mainly circulates in america, and h3n2 civ mainly circulates in asia. however, there was an outbreak of the asian h3n2 virus in the united states (us) in 2015. thus, it is important to evaluate the presence of subtype h3n8 virus in dogs in china. from may 2015 to november 2015, 600 sera from pet dogs were collected from guangzhou, shanghai, beijing and shenzhen for hemagglutination inhibition (hi) a ...201627414031
persistent infection of drug-resistant influenza a virus during chemotherapy for malignant lymphoma.we herein report the case of an 80-year-old man with malignant lymphoma who became persistently infected with influenza a virus. although he was repeatedly treated with na inhibitors, such as oseltamivir or peramivir, nasal cavity swab tests for influenza a antigen continued to be positive for more than 2 months. virological analyses revealed that he was infected with the na inhibitor-resistant a (h3n2) virus possessing an r292k substitution in the na protein. these findings suggest that a drug- ...201627374689
influenza vaccine effectiveness against antigenically drifted influenza higher than expected in hospitalized adults: 2014-2015.the 2014-2015 influenza season was severe, with circulating influenza a (h3n2) viruses that were antigenically drifted from the vaccine virus. reported vaccine effectiveness (ve) estimates from ambulatory care settings were markedly decreased.201627369320
in vitro neuraminidase inhibitory concentration (ic50) of four neuraminidase inhibitors against clinical isolates of the influenza viruses circulating in the 2010-2011 to 2014-2015 japanese influenza seasons.to assess the extent of viral resistance to the four neuraminidase inhibitors (nais), we measured their 50% inhibitory concentration (ic50) for influenza virus isolates from the 2014-2015 influenza season for comparison with those circulating in the 2010-2011 to 2013-2014 influenza seasons. viral isolation was done with specimens obtained prior to treatment, and the type and subtype of influenza was determined by rt-pcr using type- and subtype-specific primers. the ic50 was determined by a neura ...201627346379
introduction, evolution, and dissemination of influenza a viruses in exhibition swine in the united states during 2009 to 2013.the swine-human interface created at agricultural fairs, along with the generation of and maintenance of influenza a virus diversity in exhibition swine, presents an ongoing threat to public health. nucleotide sequences of influenza a virus isolates collected from exhibition swine in ohio (n = 262) and indiana (n = 103) during 2009 to 2013 were used to investigate viral evolution and movement within this niche sector of the swine industry. phylogenetic and bayesian analyses were employed to iden ...201627681134
antiviral spirotriscoumarins a and b: two pairs of oligomeric coumarin enantiomers with a spirodienone-sesquiterpene skeleton from toddalia asiatica.two pairs of oligomeric coumarin enantiomers, spirotriscoumarin a [(+)-1 and (-)-1] and spirotriscoumarin b [(+)-2 and (-)-2], with a spirodienone-sesquiterpene fused skeleton were isolated from toddalia asiatica. their structures were unambiguously established using spectroscopic data, x-ray diffraction analysis, and the electronic circular dichroism (ecd) method. the racemic mixtures (±)-1 and (±)-2 exhibit 3-to-6-fold stronger antiviral activity against influenza virus a (h3n2) (ic50: 3.13 an ...201627673343
functionalized magnetic microparticle-based colorimetric platform for influenza a virus detection.a colorimetric platform for influenza a virus detection was developed by using the high efficiency of enzymatic catalysis and the reduction of gold ions with hydrogen peroxide. aptamer-functionalized magnetic microparticles were synthesized to capture the influenza a virus. this was followed by the binding of cona-gox-aunps to the h3n2 virus through the cona-glycan interaction. the sandwich complex was subsequently dispersed in glucose solution to trigger an enzymatic reaction to produce hydroge ...201627655150
long-term adaptation of the influenza a virus by escaping cytotoxic t-cell recognition.the evolutionary adaptation of the influenza a virus (iav) to human antibodies is well characterised. much less is known about the long-term evolution of cytotoxic t lymphocyte (ctl) epitopes, which are important antigens for clearance of infection. we construct an antigenic map of iavs of all human subtypes using a compendium of 142 confirmed ctl epitopes, and show that iav evolved gradually in the period 1932-2015, with infrequent antigenic jumps in the h3n2 subtype. intriguingly, the number o ...201627629812
dynamic convergent evolution drives the passage adaptation across 48 years' history of h3n2 influenza evolution.influenza viruses are often propagated in a diverse set of culturing media and additional substitutions known as passage adaptation can cause extra evolution in the target strain, leading to ineffective vaccines. using 25,482 h3n2 ha1 sequences curated from global initiative on sharing all influenza data and national center for biotechnology information databases, we found that passage adaptation is a very dynamic process that changes over time and evolves in a seesaw like pattern. after crossin ...201627604224
primer development to obtain complete coding sequence of ha and na genes of influenza a/h3n2 virus.influenza is an acute respiratory illness and has become a serious public health problem worldwide. the need to study the ha and na genes in influenza a virus is essential since these genes frequently undergo mutations. this study describes the development of primer sets for rt-pcr to obtain complete coding sequence of hemagglutinin (ha) and neuraminidase (na) genes of influenza a/h3n2 virus from indonesia. the primers were developed based on influenza a/h3n2 sequence worldwide from global initi ...201627576569
phenotypic and genotypic analysis of influenza viruses isolated from adult subjects during a phase ii study of intravenous zanamivir in hospitalised subjects.intravenous zanamivir (ivz) is a neuraminidase (na) inhibitor (nai) under investigation for the treatment of subjects hospitalised with influenza. the study included 130 symptomatic, hospitalised adults with influenza. subjects received ivz for 5-10 days. viruses were cultured and analysed for susceptibility to zanamivir. mean ic50s (n = 50) (±sd) for influenza a/h1n1pdm09, a/h3n2 and influenza b were 0.20 ± 0.06, 0.26 ± 0.07 and 1.61 ± 0.35 nm, respectively, and are comparable to data observed ...201627568923
influenza-like illness outbreaks in nursing homes in corsica, france, 2014-2015: epidemiological and molecular characterization.to study the molecular epidemiology of the influenza outbreaks in nursing homes (nhs) to determine whether multiple influenza strains were involved.201627563533
cell-mediated immunity against antigenically drifted influenza a(h3n2) viruses in children during a vaccine mismatch season.emergence of antigenically drifted influenza a(h3n2) viruses resulted in reduced vaccine effectiveness in all age groups during the 2014-2015 influenza season. in children, inactivated influenza vaccine (iiv) elicited neutralizing antibodies (abs) against drifted strains at significantly lower levels than against the vaccine strain. little is known about the cross-reactivity of cell-mediated immunity against drifted strains in children.201627534687
[prevalence characteristics of influenza viruses in children in beijing during 2014-2015 and 2015-2016 influenza seasons].to compare the prevalence characteristics of influenza viruses in children in beijing during 2014-2015 and 2015-2016 influenza seasons.201627510869
incorporating structure context of ha protein to improve antigenicity calculation for influenza virus a/h3n2.the rapid and consistent mutation of influenza requires frequent evaluation of antigenicity variation among newly emerged strains, during which several in-silico methods have been reported to facilitate the assays. in this paper, we designed a structure-based antigenicity scoring model instead of those sequence-based previously published. protein structural context was adopted to derive the antigenicity-dominant positions, as well as the physic-chemical change of local micro-environment in corre ...201627498613
immunogenicity and protective efficacy of recombinant fusion proteins containing spike protein of infectious bronchitis virus and hemagglutinin of h3n2 influenza virus in chickens.infectious bronchitis (ib) is an acute and highly contagious viral respiratory disease of chickens and vaccination is the main method for disease control. the s1 protein, which contains several virus neutralization epitopes, is considered to be a target site of vaccine development. however, although protective immune responses could be induced by recombinant s1 protein, the protection rate in chickens was still low (<50%). here, we generated fused s1 proteins with ha2 protein (rs1-ha2) or transm ...201627497621
population genetic processes affecting the mode of selective sweeps and effective population size in influenza virus h3n2.human influenza virus a/h3n2 undergoes rapid adaptive evolution in response to host immunity. positively selected amino acid substitutions have been detected mainly in the hemagglutinin (ha) segment. the genealogical tree of ha sequences sampled over several decades comprises a long trunk and short side branches, which indicates small effective population size. various studies have reproduced this unique genealogical structure by modeling recurrent positive selection. however, it has not been cl ...201627487769
influenza a virus in backyard pigs and poultry in rural cambodia.surveillance of influenza virus in humans and livestock is critical, given the worldwide public health threats and livestock production losses. livestock farming involving close proximity between humans, pigs and poultry is often practised by smallholders in low-income countries and is considered an important driver of influenza virus evolution. this study determined the prevalence and genetic characteristics of influenza a virus (iav) in backyard pigs and poultry in cambodia. a total of 751 ani ...201627484711
recognition of influenza h3n2 variant virus by human neutralizing antibodies.since 2011, over 300 human cases of infection, especially in exposed children, with the influenza a h3n2 variant (h3n2v) virus that circulates in swine in the us have been reported. the structural and genetic basis for the lack of protection against h3n2v induced by vaccines containing seasonal h3n2 antigens is poorly understood. we isolated 17 human monoclonal antibodies (mabs) that neutralized h3n2v virus from subjects experimentally immunized with an h3n2v candidate vaccine. six mabs exhibite ...201627482543
phylodynamics of influenza a(h3n2) in south america, 1999-2012.the limited influenza a(h3n2) genetic data available from the southern hemisphere (particularly from africa and latin america), constrains the accurate reconstruction of viral dissemination dynamics within those regions. our objective was to describe the spatial dissemination dynamics of influenza a(h3n2) within south america. a total of 469 sequences of the ha1 portion of the hemagglutinin gene (ha) from influenza a(h3n2) viruses sampled in temperate and tropical south american countries betwee ...201627275847
phylogenetic analysis and pathogenicity of h3 subtype avian influenza viruses isolated from live poultry markets in china.h3 subtype influenza a virus is one of the main subtypes that threats both public and animal health. however, the evolution and pathogenicity of h3 avian influenza virus (aiv) circulating in domestic birds in china remain largely unclear. in this study, seven h3 aivs (four h3n2 and three h3n8) were isolated from poultry in live poultry market (lpm) in china. phylogenetic analyses of full genomes showed that all viruses were clustered into eurasian lineage, except n8 genes of two h3n8 isolates fe ...201627270298
are atypical lymphocytes present with viral influenza-like illnesses (ilis) in hospitalized adults?the purpose of this investigation was to determine if atypical lymphocytes were of diagnostic value in viral influenza-like illnesses (ilis) in hospitalized adults during the influenza season. are atypical lymphocytes present with viral ilis in hospitalized adults? during the influenza season, hospitals are inundated with influenza and viral ilis, e.g., human parainfluenza virus-3 (hpiv-3). without specific testing, clinically, it is difficult to differentiate influenza from ilis, and surrogate ...201627250631
enhanced catalytic activity of gold nanoparticle-carbon nanotube hybrids for influenza virus detection.multifunctional nanohybrids have created new and valuable opportunities for a wide range of catalysis and biotechnology applications. here, we present a relatively simple method for producing nanohybrids composed of gold nanoparticles (au nps) and carbon nanotubes (cnts) that does not require an acidic pre-treatment of the cnts. transmission electron microscopy (tem) images and ultraviolet-visible (uv-vis) spectra revealed that au nps bonded to the cnt surface. surface-enhanced raman scattering ...201627209577
enhanced genetic characterization of influenza a(h3n2) viruses and vaccine effectiveness by genetic group, 2014-2015.during the 2014-2015 us influenza season, expanded genetic characterization of circulating influenza a(h3n2) viruses was used to assess the impact of the genetic variability of influenza a(h3n2) viruses on influenza vaccine effectiveness (ve).201627190176
phylodynamics with migration: a computational framework to quantify population structure from genomic data.when viruses spread, outbreaks can be spawned in previously unaffected regions. depending on the time and mode of introduction, each regional outbreak can have its own epidemic dynamics. the migration and phylodynamic processes are often intertwined and need to be taken into account when analyzing temporally and spatially structured virus data. in this article, we present a fully probabilistic approach for the joint reconstruction of phylodynamic history in structured populations (such as geogra ...201627189573
co-delivery of gpi-anchored ccl28 and influenza ha in chimeric virus-like particles induces cross-protective immunity against h3n2 viruses.influenza infection typically initiates at respiratory mucosal surfaces. induction of immune responses at the sites where pathogens initiate replication is crucial for the prevention of infection. we studied the adjuvanticity of gpi-anchored ccl28 co-incorporated with influenza ha-antigens in chimeric virus-like particles (cvlps), in boosting strong protective immune responses through an intranasal (i.n.) route in mice. we compared the immune responses to that from influenza vlps without ccl28, ...201627178810
first documented case of influenza a (h3n2 subtype) infection in a patient with complete interferon gamma receptor 1 deficiency: a call for systemic vaccination strategies. 201627171582
enhanced replication of avian-origin h3n2 canine influenza virus in eggs, cell cultures and mice by a two-amino acid insertion in neuraminidase stalk.canine influenza virus (civ) is a newly identified, highly contagious respiratory pathogen in dogs. recent studies indicate that avian-origin h3n2 civ are circulating in chinese dogs. to investigate the effects of a two-amino acid (2-aa) insertion naturally occurring at the distal end of the neuraminidase (na) stalk found in chinese isolates since 2010 on virus replication and virulence, we rescued the civ strain, a/canine/jiangsu/06/2011(h3n2) and its na mutant without the 2-aa insertion using ...201627160077
seasonal influenza a/h3n2 virus infection and il-1β, il-10, il-17, and il-28 polymorphisms in iranian population.increased blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza a/h3n2 virus infection. the study was aimed to investigate the polymorphisms of il-1β, il-10, il-17, and il-28 genes to find the possibility of their association with the clinical outcome of influenza a/h3n2 virus infection among the infected patients in iran. this is a case-control study in which influenza a/h3n2 virus positive confirmed with real-time pcr were ...201627155288
predac-h3: a user-friendly platform for antigenic surveillance of human influenza a(h3n2) virus based on hemagglutinin sequences.timely surveillance of the antigenic dynamics of the influenza virus is critical for accurate selection of vaccine strains, which is important for effective prevention of viral spread and infection.201627153622
characterization of influenza activity based on virological surveillance of influenza-like illness in tropical singapore, 2010-2014.singapore is situated in the tropics where the seasonality of influenza is not as well defined as that of temperate countries. we examined the circulation of influenza viruses in the community in terms of the characteristics of influenza activity. we reviewed laboratory-confirmed virological data collected between 2010 and 2014 under the national influenza surveillance programme. influenza activity was measured by the proportion of specimens from outpatients with influenza-like illness tested po ...201627152935
genetic and antigenic characterization of hemagglutinin of influenza a/h3n2 virus from the 2015 season in thailand.antigenic changes in the ha1 domain of the influenza a/h3n2 hemagglutinin (ha) present a challenge in the design of the annual influenza vaccine. we examined the genetic variability in the nucleotide and amino acid of encoding ha1 sequences of the influenza a/h3n2 virus during the 2015 influenza season in thailand. toward this, the ha genes of 45 influenza a/h3n2 strains were amplified and sequenced. although a clade 3c.3a strain (a/switzerland/9715293/2013) was chosen for the 2015 vaccine, phyl ...201627146171
the avian-origin h3n2 canine influenza virus that recently emerged in the united states has limited replication in swine.equine-origin h3n8 has circulated in dogs in the united states since 1999. a genetically and antigenically distinct avian-origin h3n2 canine influenza was detected in march of 2015 in chicago, illinois. subsequent outbreaks were reported with over 1000 dogs in the midwest affected followed by 23 additional states with detections within 5 months. the potential for canine-to-swine transmission was unknown. experimental infection in pigs showed this virus does not replicate efficiently in swine.201627110913
factors associated with poor outcomes among adults hospitalized for influenza in france: a three-year prospective multicenter study.influenza is an important cause of serious illness and death, particularly in elderly and high-risk groups.201627105315
influenza vaccine effectiveness in preventing hospitalizations with laboratory-confirmed influenza in greece during the 2014-2015 season: a test-negative study.the 2014-2015 influenza season was marked by circulation of antigenically drifted a/h3n2 strains, raising the possibility of low seasonal influenza vaccine effectiveness (ve). we assessed ve against hospitalization with laboratory-confirmed influenza for the 2014-2015 season, using routine surveillance data. non-sentinel swab samples from greek hospital inpatients were tested for influenza by rt-pcr in three laboratories, covering the entire country. we estimated ve using a test-negative design. ...201627088266
prolonged intermittent virus shedding during an outbreak of canine influenza a h3n2 virus infection in dogs in three chicago area shelters: 16 cases (march to may 2015).objective to estimate an appropriate isolation period for dogs infected with canine influenza a h3n2 virus on the basis of the duration of virus shedding. design retrospective case series. animals 16 dogs, from 3 chicago area shelters, naturally infected with canine influenza a h3n2 virus. procedures medical records of 16 affected dogs were reviewed. nasal swab specimens from each dog had been tested periodically for a minimum of 15 days following an initial positive real-time reverse transcript ...201627074610
susceptibility of influenza viruses circulating in western saudi arabia to neuraminidase inhibitors.to investigate the sensitivity of circulating influenza viruses in western saudi arabia to neuraminidase inhibitors (nais); mainly, zanamivir and oseltamivir.201627052292
[successful treatment of seasonal influenza a (h3n2) infection-related hemophagocytic lymphocytosis in an elderly man].a 79-year-old man experienced severe chronic obstructive pulmonary disease (copd) and was receiving treatment for ischemic heart disease. starting from dizziness and chilliness, he lost consciousness after few days. he was taken to our emergency department. on initial evaluation, he complained of dyspnea and was afebrile with a pulse rate, blood pressure, and respiratory rate of 105 beats/min, 112/98mmhg, and 28 breath/min, respectively. his respiratory sounds were clear and chest radiography di ...201627032178
waning protection of influenza vaccine against mild laboratory confirmed influenza a(h3n2) and b in spain, season 2014-15.the 2014/15 influenza season in spain was dominated by the circulation of drifted a(h3n2) and co-circulation of b viruses. we present the final estimates of influenza vaccine effectiveness (ive) against confirmed influenza a(h3n2) and b its evolution along the season and with time since vaccination.201627020713
genetic characterization of an ancestral strain of the avian-origin h3n2 canine influenza virus currently circulating in east asia.h3n2 canine influenza virus emerged in south korea in 2007 and subsequently spread to china and thailand, causing epidemic or endemic respiratory diseases in dogs. through intermammalian species transmission, the virus has also infected cats. however, no direct evidence of significant genetic evolution has been reported since its first emergence. here, we describe in depth the genetic and molecular characteristics of the ancestral strain (i.e., the first virus isolate from south korea) of the h3 ...201627012241
characterization of a novel h3n2 influenza virus isolated from domestic ducks in china.cases of human infection with a novel h7n9 avian influenza virus (aiv) were first reported in march 2013, which caused 115 deaths within a single year. beyond that, other subtypes of h7 aiv were isolated from poultry in eastern china during the same period, including h7n7 and h7n2 aiv. in the present study, a subtype h3n2 aiv was isolated from ducks from anhui province, china. sequence and phylogenetic analyses revealed that seven gene segments of this virus showed the highest sequence homology ...201627000112
a plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and t cell response in healthy adults.recent issues regarding efficacy of influenza vaccines have re-emphasized the need of new approaches to face this major public health issue. in a phase 1-2 clinical trial, healthy adults received one intramuscular dose of a seasonal influenza plant-based quadrivalent virus-like particle (qvlp) vaccine or placebo. the hemagglutination inhibition (hi) titers met all the european licensure criteria for the type a influenza strains at the 3μg/strain dose and for all four strains at the higher dosage ...201626987887
cooperation between distinct viral variants promotes growth of h3n2 influenza in cell culture.rna viruses rapidly diversify into quasispecies of related genotypes. this genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. here, we demonstrate strong cooperation between two h3n2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. residue 151 is often annotated as an ambiguous amino acid i ...201626978794
effects of egg-adaptation on receptor-binding and antigenic properties of recent influenza a (h3n2) vaccine viruses.influenza a virus (subtype h3n2) causes seasonal human influenza and is included as a component of influenza vaccines. the majority of vaccine viruses are isolated and propagated in eggs, which commonly results in amino acid substitutions in the haemagglutinin (ha) glycoprotein. these substitutions can affect virus receptor-binding and alter virus antigenicity, thereby, obfuscating the choice of egg-propagated viruses for development into candidate vaccine viruses. to evaluate the effects of egg ...201626974849
influenza vaccine manufacturing: effect of inactivation, splitting and site of manufacturing. comparison of influenza vaccine production processes.the aim of this study was to evaluate the impact of different inactivation and splitting procedures on influenza vaccine product composition, stability and recovery to support transfer of process technology. four split and two whole inactivated virus (wiv) influenza vaccine bulks were produced and compared with respect to release criteria, stability of the bulk and haemagglutinin recovery. one clarified harvest of influenza h3n2 a/uruguay virus prepared on 25.000 fertilized eggs was divided equa ...201626959983
prediction, dynamics, and visualization of antigenic phenotypes of seasonal influenza viruses.human seasonal influenza viruses evolve rapidly, enabling the virus population to evade immunity and reinfect previously infected individuals. antigenic properties are largely determined by the surface glycoprotein hemagglutinin (ha), and amino acid substitutions at exposed epitope sites in ha mediate loss of recognition by antibodies. here, we show that antigenic differences measured through serological assay data are well described by a sum of antigenic changes along the path connecting viruse ...201626951657
vaccination with 2014-15 seasonal inactivated influenza vaccine elicits cross-reactive anti-ha antibodies with strong adcc against antigenically drifted circulating h3n2 virus in humans.it is well established that virus neutralizing (vn) antibodies to hemagglutinin (ha) antigens of influenza a viruses provide optimal protection against antigenically matched strains of influenza a viruses. in contrast, little is known about the potential role of ha-specific, non-neutralizing antibodies in protection against human influenza illness at present. in this study, we show that individuals vaccinated with the 2014-15 seasonal inactivated influenza vaccine displayed strong a/h3n2 ha-spec ...201626950058
influenza h3n2 infection of the collaborative cross founder strains reveals highly divergent host responses and identifies a unique phenotype in cast/eij mice.influenza a virus is a zoonotic pathogen that poses a major threat to human and animal health. the severe course of influenza infection is not only influenced by viral virulence factors but also by individual differences in the host response. to determine the extent to which the genetic background can modulate severity of an infection, we studied the host responses to influenza infections in the eight genetically highly diverse collaborative cross (cc) founder mouse strains.201626921172
new england harbor seal h3n8 influenza virus retains avian-like receptor specificity.an influenza h3n8 virus, carrying mammalian adaptation mutations, was isolated from new england harbor seals in 2011. we sought to assess the risk of its human transmissibility using two complementary approaches. first, we tested the binding of recombinant hemagglutinin (ha) proteins of seal h3n8 and human-adapted h3n2 viruses to respiratory tissues of humans and ferrets. for human tissues, we observed strong tendency of the seal h3 to bind to lung alveoli, which was in direct contrast to the hu ...201626888262
conserved stem fragment from h3 influenza hemagglutinin elicits cross-clade neutralizing antibodies through stalk-targeted blocking of conformational change during membrane fusion.currently available influenza vaccines typically fail to elicit/boost broadly neutralizing antibodies due to the mutability of virus sequences and conformational changes during protective immunity, thereby limiting their efficacy. this problem needs to be addressed by further understanding the mechanisms of neutralization and finding the desired neutralizing site during membrane fusion. this study specifically focused on viruses of the h3n2 subtype, which have persisted as a principal source of ...201626875772
comparison of as03 and alum on immune responses elicited by a/h3n2 split influenza vaccine in young, mature and aged balb/c mice.there is great interest in developing more effective influenza vaccines for the elderly. oil-in-water adjuvants can boost humoral responses to seasonal vaccines in elderly subjects but relatively little is known about their mechanism of action.201626873056
directed selection of influenza virus produces antigenic variants that match circulating human virus isolates and escape from vaccine-mediated immune protection.influenza vaccination does not provide 100% protection from infection, partly due to antigenic drift of the haemagglutinin (ha) protein. low serum antibody titres increase the risk of infection. to determine whether there were additional correlates of risk, we examined the relationship between human serum immunity and antigenic variation in seasonal h3n2 influenza viruses. seasonal h3n2 vaccine strains grown in the presence of heterogeneous human or mono-specific ferret antisera selected variant ...201626854888
mutations acquired during cell culture isolation may affect antigenic characterisation of influenza a(h3n2) clade 3c.2a viruses.as elsewhere, few (< 15%) sentinel influenza a(h3n2) clade 3c.2a viruses that dominated in canada during the 2014/15 season could be antigenically characterised by haemagglutination inhibition (hi) assay. clade 3c.2a viruses that could be hi-characterised had acquired genetic mutations during in vitro cell culture isolation that modified the potential glycosylation motif found in original patient specimens and the consensus sequence of circulating viruses at amino acid positions 158-160 of the h ...201626836031
heptapeptide ligands against receptor-binding sites of influenza hemagglutinin toward anti-influenza therapy.the initial attachment of influenza virus to cells is the binding of hemagglutinin (ha) to the sialyloligosaccharide receptor; therefore, the small molecules that inhibit the sugar-protein interaction are promising as ha inhibitors to prevent the infection. we herein demonstrate that sialic acid-mimic heptapeptides are identified through a selection from a primary library against influenza virus ha. in order to obtain lead peptides, an affinity selection from a phage-displayed random heptapeptid ...201626833245
[the specific features of the cocirculation of influenza viruses in the 2010-2011 postpandemic period according to the results of activities of the d. i. ivanovsky research institute of virology, ministry of health and social development of russia].the paper gives the results of monitoring the circulation of influenza viruses in the 2010-2011 season, that covers the second year of circulation of pandemic a(h1n1)v virus strains, and their interaction with seasonal a (h3n2) and b strains. unlike the previous season, the beginning of an increase in morbidity was recorded in january 2011; its peak in the most of contiguous areas was noted at 5-7 weeks of 2011, with its further decline to threshold levels at week 11 of 2011. preschool and schoo ...201622624469
[cold-adapted a/krasnodar/101/35/59 (h2n2) strain--a promising strain-donor of attenuation for procuration of live influenza vaccines].study of ts, ca, att phenotype, immunogenicity and protective effectiveness of reassortants obtained by a way of recombination of a new influenza cold-adapted (ca) strain donor of attenuation a/krasnodar/101/35/59 (h2n2) and virulent strain of influenza virus.201626829850
recombinant influenza virus with a pandemic h2n2 polymerase complex has a higher adaptive potential than one with seasonal h2n2 polymerase complex.the reassortment of influenza viral gene segments plays a key role in the genesis of pandemic strains. all of the last three pandemic viruses contained reassorted polymerase complexes with subunits derived from animal viruses, suggesting that the acquisition of a reassorted polymerase complex might have a role in generating these pandemic viruses. here, we studied polymerase activities of the pandemic h2n2, seasonal h2n2 and pandemic h3n2 viruses. we observed that the viral ribonucleoprotein (vr ...201626703222
[differential diagnosis of the viral etiology of suspected mumps in a population with high vaccine coverage].in this study, buccal swabs from patients with the clinical picture of parotitis epidemica in whom mumps virus (mv) infection was not confirmed by direct detection or serologically were tested. the aim was to detect by molecular methods nucleic acids (nas) of other respiratory viruses possibly involved in salivary gland swelling. at the same time, paired sera, if available, were tested.201628078898
frequency of influenza h3n2 intra-subtype reassortment: attributes and implications of reassortant spread.increasing evidence suggests that influenza reassortment not only contributes to the emergence of new human pandemics but also plays an important role in seasonal influenza epidemics, disease severity, evolution, and vaccine efficacy. we studied this process within 2091 h3n2 full genomes utilizing a combination of the latest reassortment detection tools and more conventional phylogenetic analyses.201628034300
detection of d151g/n mutations in the neuraminidase gene of influenza a (h3n2) viruses by real-time rt-pcr allelic discrimination assay.single nucleotide polymorphisms (snps) at d151 position of neuraminidase (na) gene of influenza a (h3n2) virus has been associated with drug resistance and increased binding affinity. na-d151g/n-substitutions of influenza a (h3n2) viruses are frequently induced and selected by culturing in madin-darby canine kidney (mdck) cell lines. it is important to consider and exclude d151g/n mutants after isolation of influenza virus in mdck cell line; since, the substitutions can highly influence the resu ...201628004398
activity of ergoferon against lethal influenza a (h3n2) virus infection in mice.the influenza a virus accounts for serious annual viral upper respiratory tract infections. it is constantly able to modify its antigenic structure, thus evading host defence mechanisms. moreover, currently available anti-influenza agents have a rather limited application, emphasizing the further need for new effective treatments. one of them is ergoferon, a drug containing combined polyclonal antibodies - anti-interferon gamma, anti-cd4 receptor and anti-histamine - in released-active form. the ...201627924780
efficacy of clarithromycin-naproxen-oseltamivir combination in the treatment of patients hospitalized for influenza a(h3n2) infection: an open-label, randomized controlled, phase 2b/3 trial.influenza causes excessive hospitalizations and deaths. single agent treatment with oseltamivir in severe influenza might be insufficient. the study assessed the efficacy and safety of oseltamivir-clarithromycin-naproxen combination for treatment of serious influenza.201627884765
combinations of 1,8-cineol and oseltamivir for the treatment of influenza virus a (h3n2) infection in mice.it is need for development of new means against influenza virus due to the lack of efficacy of available therapeutic strategies. in previous research, 1,8-cineol exert its inhibition of nuclear factor (nf)-κb, the main regulator of cytokine and chemokine production in influenza, and anti-inflammatory activity. these fact supports and helps establish the hypothesis that 1,8-cineol may have synergism with an antiviral on influenza virus infection. the combined effect of 1,8-cineol with oseltamivir ...201627966790
incidence of medically attended influenza among residents of shai-osudoku and ningo-prampram districts, ghana, may 2013 - april 2015.influenza vaccination is recommended by the world health organization for high risk groups, yet few data exist on influenza disease burden in west africa.201627964716
glycosylation changes in the globular head of h3n2 influenza hemagglutinin modulate receptor binding without affecting virus virulence.since the emergence of human h3n2 influenza a viruses in the pandemic of 1968, these viruses have become established as strains of moderate severity. a decline in virulence has been accompanied by glycan accumulation on the hemagglutinin globular head, and hemagglutinin receptor binding has changed from recognition of a broad spectrum of glycan receptors to a narrower spectrum. the relationship between increased glycosylation, binding changes, and reduction in h3n2 virulence is not clear. we eva ...201627796371
outbreak of influenza a(h3n2) variant virus infections among persons attending agricultural fairs housing infected swine - michigan and ohio, july-august 2016.on august 3, 2016, the ohio department of health laboratory reported to cdc that a respiratory specimen collected on july 28 from a male aged 13 years who attended an agricultural fair in ohio during july 22-29, 2016, and subsequently developed a respiratory illness, tested positive by real-time reverse transcription-polymerase chain reaction (rrt-pcr) for influenza a(h3n2) variant* (h3n2v). the respiratory specimen was collected as part of routine influenza surveillance activities. the next day ...201627787493
trivalent inactivated influenza vaccine effective against influenza a(h3n2) variant viruses in children during the 2014/15 season, japan.the 2014/15 influenza season in japan was characterised by predominant influenza a(h3n2) activity; 99% of influenza a viruses detected were a(h3n2). subclade 3c.2a viruses were the major epidemic a(h3n2) viruses, and were genetically distinct from a/new york/39/2012(h3n2) of 2014/15 vaccine strain in japan, which was classified as clade 3c.1. we assessed vaccine effectiveness (ve) of inactivated influenza vaccine (iiv) in children aged 6 months to 15 years by test-negative case-control design ba ...201627784529
il-2 and il-6 cooperate to enhance the generation of influenza-specific cd8 t cells responding to live influenza virus in aged mice and humans.an age-related decline in cytolytic activity has been described in cd8+ t cells and we have previously shown that the poor cd8+ effector t cell responses to influenza a/h3n2 challenge result from a decline in the proportion and function of these cytolytic t lymphocytes (ctl). here, we describe that addition of exogenous cytokines to influenza-stimulated pbmc from both aged mice and humans, enhances the generation of influenza specific cd8 ctl by increasing their proliferation and survival. our d ...201627322555
seasonal influenza vaccine (a/new york/39/2012) effectiveness against influenza a virus of health care workers in a long term care facility attached with the hospital, japan, 2014/15: a cohort study.the 2014/15 influenza season started earlier than usual, and intense activity was reflection of circulation of antigenically-drifted and vaccine-mismatched dominant a(h3n2) viruses. although inpatients and health-care workers (hcws) had a high influenza vaccination coverage rate well prior to the beginning of influenza season, numerous outbreaks of influenza a(h3n2) infection with fatal cases were reported in long-term care facilities (ltcfs) in japan during 2014/15 influenza season. in january ...201627118211
activities of jnj63623872 and oseltamivir against influenza a h1n1pdm and h3n2 virus infections in mice.jnj63623872 (formerly known as vx-787) is an inhibitor of influenza a virus polymerases through interaction with the viral pb2 subunit. this interaction blocks the cap-snatching activity of the virus that is essential for virus replication. previously published work has documented antiviral activity of jnj63623872 in cell culture and mouse infection studies. in this report, we extend the in vivo observations by comparing the efficacies of jnj63623872 and oseltamivir in mice infected with influen ...201627771390
canine h3n8 influenza vaccines partially protect mice against the canine h3n2 strain currently circulating in the united states.influenza a viruses infect many species and cross-species transmission occurs occasionally. an equine h3n8 influenza virus began circulating in dogs in 1999 and an avian h3n2 influenza virus began circulating in dogs in 2006. the canine h3n8 (ch3n8) viral strain has become endemic in parts of the united states and there is a commercially available vaccine against this strain. the canine h3n2 (ch3n2) strain did not circulate widely in the united states until 2015. here, we used a mouse model to d ...201627670073
viral fusion efficacy of specific h3n2 influenza virus reassortant combinations at single-particle level.virus pseudotyping is a useful and safe technique for studying entry of emerging strains of influenza virus. however, few studies have compared different reassortant combinations in pseudoparticle systems, or compared entry kinetics of native viruses and their pseudotyped analogs. here, vesicular stomatitis virus (vsv)-based pseudovirions displaying distinct influenza virus envelope proteins were tested for fusion activity. we produced vsv pseudotypes containing the prototypical x-31 (h3) ha, ei ...201627752100
incidence of influenza virus-associated severe acute respiratory infection in damanhour district, egypt, 2013.the epidemiology, seasonality and risk factors for influenza virus infection remains poorly defined in countries such as egypt. between 1 january and 31 december 2013, we used surveillance data on patients hospitalized with severe acute respiratory infection in three egyptian government hospitals in damanhour district to estimate the incidence rate of laboratory-confirmed seasonal influenza. samples were taken from 1727 of 1856 patients; of these, 19% were influenza virus positive. the overall i ...201627714745
sequence amplification via cell passaging creates spurious signals of positive adaptation in influenza virus h3n2 hemagglutinin.clinical influenza a virus isolates are frequently not sequenced directly. instead, a majority of these isolates (~70% in 2015) are first subjected to passaging for amplification, most commonly in non-human cell culture. here, we find that this passaging leaves distinct signals of adaptation, which can confound evolutionary analyses of the viral sequences. we find distinct patterns of adaptation to madin-darby (mdck) and monkey cell culture absent from unpassaged hemagglutinin sequences. these p ...201627713835
2014-2015 influenza vaccine effectiveness in the united states by vaccine type.circulating a/h3n2 influenza viruses drifted significantly after strain selection for the 2014-2015 vaccines. also in 2014-2015, the advisory committee on immunization practices recommended preferential use of live attenuated influenza vaccine (laiv) over inactivated influenza vaccine (iiv) among children aged 2-8 years.201627702768
viral inhibition of bacterial phagocytosis by human macrophages: redundant role of cd36.macrophages are essential to maintaining lung homoeostasis and recent work has demonstrated that influenza-infected lung macrophages downregulate their expression of the scavenger receptor cd36. this receptor has also been shown to be involved in phagocytosis of streptococcus pneumoniae, a primary agent associated with pneumonia secondary to viral infection. the aim of this study was to investigate the role of cd36 in the effects of viral infection on macrophage phagocytic function. human monocy ...201627701435
[influenza virus reproduction in the endothelial cells of human blood vessels].the current epidemic strains of the influenza subtypes y5n1, h3n2, and h1n1 can be reproduced in the cultured human endothelial eahy926 cells with an infective activity of 3.0-4.5 ig tcd50. these findings were confirmed by the analysis of the autopsy material from patients who had died from influenza during the 2009-2010 epidemic, which showed influenza virus ha and np proteins in the pulmonary blood vascular endothelium. the results obtained reflect a new aspect of the pathogenesis of influenza ...201622834142
[interaction of influenza a and b viruses with nanodiamond-based sorbents].the paper presents data on the sorption of influenza a(h1n1), a(h1n1)v, a(h3n2) viruses, cdna of a(h1n1)v and b viruses on nanodiamonds and furnace charge. the sorption of viruses occurred in different solutions at 4-37 degrees c during 10-20 min. the rate of sorption varied with the concentration of a sorbent in the solution and its structure, but did not with the antigenic formula of viruses or temperature. the sorption capacity of furnace charge towards influenza a and b viruses was higher th ...201622834140
[the peculiarities of the influenza epidemics in some areas of russia during 2012-2013 season. the influenza a (h1n1) pdm09 virus domination in european countries].the peculiarities of the influenza viruses circulation in 2012-2013 are discussed. the results were obtained in 10 cities of russia, where basic laboratories of the influenza ecology and epidemics center of on the basis of ivanovsky institute of virology, ministry of health of the russian federation, are situated. the increasing rate of the ard morbidity caused by influenza viruses was observed in january-march 2013. the highest indices of the morbidity were detected during 6-7 weeks with the fo ...201625069278
evaluation of screening assays for the detection of influenza a virus serum antibodies in swine.increased surveillance of influenza a virus (iav) infections in human and swine populations is mandated by public health and animal health concerns. antibody assays have proven useful in previous surveillance programmes because antibodies provide a record of prior exposure and the technology is inexpensive. the objective of this research was to compare the performance of influenza serum antibody assays using samples collected from pigs (vaccinated or unvaccinated) inoculated with either a/swine/ ...201624571447
[local antibody immune responses in influenza patients and persons vaccinated with seasonal, pre-pandemic, and pandemic live attenuated influenza vaccines].mucosal immunity is one of the most important factors of human anti-influenza defense. the data about local immune responses in influenza a (h3n2) patients and in persons vaccinated within 2000-2009 with different seasonal laivs, a (h1n1)pdm2009 laiv, and a (h5n2) laiv are discussed. the influenza infection resulted in the larger quantities of local iga and igg conversions than seasonal laiv vaccination. 56% of young (18-21 y.o.) persons had high titers (> or = 1:64) of iga to a (h1n1)pdm2009 vi ...201624006632
[the influenza viruses and their surface proteins impact on the metabolism of human blood vessel endothelium cells].the modern influenza virus subtypes h3n2, h5n1, and h1n1 reduced the metabolism of the endothelial cells within the range from 20% to 60% (compared with control). the degree of the activity of the dehydrogenase reduction depended on the dose of virus and time of virus reproduction. ha and na also actively reduced the metabolism of the cells ranging from 5% to 60%, depending on the concentration of the proteins and time of their impact on cells. neuraminidase was more active than hemagglutinin in ...201624006629
[immunogenicity of recombinant proteins including ectodomain of m2 influenza virus a].two recombinant proteins with three copies of the ectodomain of the conserved influenza protein m2 (m2e) of influenza viruses were developed: a (h1n1)pdm09, a/kurgan/05/05 (h5n1), and m2e consensus sequence of the human influenza a virus (h1n1, h2n2, h3n2) based on flagellin and core antigen of hepatitis b (hbc). the first recombinant protein comprised flagellin fused to three tandem copies of m2e, the second preparation was based on non-covalent interaction between m2e peptides and hbc. the imm ...201624006628
[humoral and cell-mediated immune responses in humans to the a/california/07/ 2009 (h1n1) virus, a(h1n1)pdm2009].during the twentieth century the world faced four influenza a pandemics: a (h1n1) in 1918, a (h2n2) in 1957, a (h3n2) in 1957 and a (h1n1) recirculation in 1977. in the beginning of 2009 the global spread of a(h1n1)pdm2009 virus was detected. in consideration of clinical evidences and genetic data analysis who declared as the novel pandemic of 21th century. however, the fact of exceedingly prolonged previous worldwide circulation of a (h1n1) influenza viruses was not taken into account. further ...201623785769
the pb1 segment of an influenza a virus h1n1 2009pdm isolate enhances the replication efficiency of specific influenza vaccine strains in cell culture and embryonated eggs.influenza vaccine strains (ivss) contain the haemagglutinin (ha) and neuraminidase (na) genome segments of relevant circulating strains in the genetic background of influenza a/pr/8/1934 virus (pr8). previous work has shown that the nature of the pb1 segment may be a limiting factor for the efficient production of ivss. here, we showed that the pb1 segment (pb1gi) from the 2009 pandemic influenza a virus (iav) a/giessen/06/2009 (gi wt, h1n1pdm) may help to resolve (some of) these limitations. we ...201626743314
deep sequencing reveals potential antigenic variants at low frequencies in influenza a virus-infected humans.influenza vaccines must be frequently reformulated to account for antigenic changes in the viral envelope protein, hemagglutinin (ha). the rapid evolution of influenza virus under immune pressure is likely enhanced by the virus's genetic diversity within a host, although antigenic change has rarely been investigated on the level of individual infected humans. we used deep sequencing to characterize the between- and within-host genetic diversity of influenza viruses in a cohort of patients that i ...201626739054
ring test evaluation of the detection of influenza a virus in swine oral fluids by real-time reverse-transcription polymerase chain reaction and virus isolation.the probability of detecting influenza a virus (iav) in oral fluid (of) specimens was calculated for each of 13 assays based on real-time reverse-transcription polymerase chain reaction (rrt-pcr) and 7 assays based on virus isolation (vi). the of specimens were inoculated with h1n1 or h3n2 iav and serially diluted 10-fold (10(-1) to 10(-8)). eight participating laboratories received 180 randomized of samples (10 replicates × 8 dilutions × 2 iav subtypes plus 20 iav-negative samples) and performe ...201626733728
quantifying influenza virus diversity and transmission in humans.influenza a virus is characterized by high genetic diversity. however, most of what is known about influenza evolution has come from consensus sequences sampled at the epidemiological scale that only represent the dominant virus lineage within each infected host. less is known about the extent of within-host virus diversity and what proportion of this diversity is transmitted between individuals. to characterize virus variants that achieve sustainable transmission in new hosts, we examined withi ...201626727660
imidazole-based pinanamine derivatives: discovery of dual inhibitors of the wild-type and drug-resistant mutant of the influenza a virus.we previously reported potent hit compound 4 inhibiting the wild-type influenza a virus a/hk/68 (h3n2) and a/m2-s31n mutant viruses a/ws/33 (h1n1), with its latter activity quite weak. to further increase its potency, a structure-activity relationship study of a series of imidazole-linked pinanamine derivatives was conducted by modifying the imidazole ring of this compound. several compounds of this series inhibited the amantadine-sensitive virus at low micromolar concentrations. among them, 33 ...201626722757
detection and pathogenesis of a novel swine h3n2 influenza virus containing three genes from the 2009 pandemic h1n1 influenza viruses in korea in 2015. 201627853991
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