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design and synthesis of 1,2,3-triazole-containing n-acyl zanamivir analogs as potent neuraminidase inhibitors.the design of potent metabolically stable neuraminidase (na) inhibitors represents an attractive approach for treating influenza virus infection. in this study, we describe the exploitation of the 150-cavity in the active site of group 1 na for the design, synthesis, and in vitro evaluation of new triazole-containing n-acyl derivatives related to zanamivir. inhibition studies with influenza virus nas of group 1 (h1n1) and group 2 (h3n2) revealed that several of them are good inhibitors, with ic5 ...201627487569
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
role of the b allele of influenza a virus segment 8 in setting mammalian host range and pathogenicity.two alleles of segment 8 (ns) circulate in nonchiropteran influenza a viruses. the a allele is found in avian and mammalian viruses, but the b allele is viewed as being almost exclusively found in avian viruses. this might reflect the fact that one or both of its encoded proteins (ns1 and nep) are maladapted for replication in mammalian hosts. to test this, a number of clade a and b avian virus-derived ns segments were introduced into human h1n1 and h3n2 viruses. in no case was the peak virus ti ...201627489273
influenza virus vaccine for neglected hosts: horses and dogs.this study provides information regarding vaccine research and the epidemiology of influenza virus in neglected hosts (horses and dogs). equine influenza virus (eiv) causes a highly contagious disease in horses and other equids, and outbreaks have occurred worldwide. eiv has resulted in costly damage to the horse industry and has the ability of cross the host species barrier from horses to dogs. canine influenza is a virus of equine or avian origin and infects companion animals that live in clos ...201627489801
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
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
[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
seroprevalence of three influenza a viruses (h1n1, h3n2, and h3n8) in pet dogs presented to veterinary hospital in ohio.the prevalence of canine h3n8 influenza, and human h1n1 and h3n2 influenza in dogs in ohio was estimated by conducting serologic tests on 1,082 canine serum samples; risk factors, such as health status and age were examined. the prevalence of human h1n1, h3n2, and canine h3n8 were 4.0%, 2.4% and 2.3%, respectively, and two samples were seropositive to two subtypes (h1n1 and h3n2; h1n1 and canine influenza virus (civ) h3n8). dogs with respiratory signs were 5.795 times more likely to be seroposit ...201627515265
the inhibitory effect of dehydroepiandrosterone and its derivatives against influenza a virus in vitro and in vivo.the antiviral activity of dehydroepiandrosterone (dhea) and 21 synthetic derivatives against influenza a virus (iav) replication was investigated in vitro in cell culture. our results revealed that three dhea analogues were potent inhibitors of iav multiplication in mdck cells and mainly blocked the post-attachment stage of viral infection. among these derivatives, one containing a 2-oh-ph moiety (3i) exhibited the best inhibitory effects against h1n1 and h3n2 iav in a dose-dependent manner. mor ...201627518401
serum amyloid a (saa) is an early biomarker of influenza virus disease in balb/c, c57bl/2, swiss-webster, and dba.2 mice.assessment of influenza virus disease progression and efficacy of antiviral therapy in the widely used mouse models relies mostly on body weight loss and lung virus titers as markers of disease. however, both parameters have their shortcomings. therefore, the aim of our study was to find non-invasive markers in the murine model of severe influenza that could detect disease early and predict disease outcome. balb/c mice were lethally infected with influenza a(h1n1)pdm09 virus and serum samples we ...201627523492
evaluation of a set of c9 n-acyl neu5ac2en mimetics as viral sialidase selective inhibitors.identification of selective influenza viral sialidase inhibitors is highly desirable in order to minimize or avoid the adverse effects due to the possible inhibition of endogenous human sialidases. we recently reported the evaluation of c9 n-acyl neu5ac2en mimetics as probes for human sialidases. herein, we describe the in vitro activity of the same set of c9 n-acyl neu5ac2en mimetics against sialidases expressed by influenza virus a/pr/8/34 (h1n1), a/memphis/1/72 (h3n2), and a/duck/313/78 (h5n3 ...201127525119
[influenza surveillance in five consecutive seasons during post pandemic period: results from national influenza center, turkey].influenza surveillance provides data about the characteristics of influenza activity, types, sub-types and antigenic properties of the influenza viruses in circulation in a region. surveillance also provides for the preparation against potential influenza pandemics with the identification of the genetic properties of viruses and the mutant strains that could pose a threat. in this study, data in the scope of national influenza surveillance carried out by national influenza center, turkey for fiv ...201627525396
[evaluation of sentinel influenza surveillance of the last two seasons: 2013-2014 and 2014-2015].flu caused by influenza viruses, is a serious public health problem all over the world with its high morbidity and mortality. therefore world health organization (who) regularly collects the results of national influenza surveillance, evaluates the results and shares them on international portal. thus, it provides the possibility of rapid prevention and preparation of countries that needs to be taken on the fight against the epidemic flu. starting from 2004-2005 season until today the current fl ...201627525397
[mutations in the neuraminidase gene of the epidemic influenza virus strain isolated in the 2012-2013 season and improvement of a pcr assay for the detection of influenza virus].in 2011, we developed a real-time rt-pcr method to rapidly and sensitively detect three subtypes of influenza a virus [h1n1, h3n2, and influenza (h1n1) 2009] and influenza b virus (the conventional pcr method). this method was useful during the 2011-2012 epidemic season. however, epidemic influenza a virus strain h3n2 in the 2012-2013 season was undetectable by this method, possibly due to mutation in the neuraminidase (na) gene of epidemic influenza a virus strain h3n2. therefore, we improved t ...201427526538
anomaly detection in host signaling pathways for the early prognosis of acute infection.clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. we present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, lipopolysaccharides (lps). using an anomaly detection framework we identified pathways that clearly disti ...201627532264
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
ns1 protein mutation i64t affects interferon responses and virulence of circulating h3n2 human influenza a viruses.influenza ns1 protein is the main viral protein counteracting host innate immune responses, allowing the virus to efficiently replicate in interferon (ifn)-competent systems. in this study, we analyzed ns1 protein variability within influenza a (iav) h3n2 viruses infecting humans during the 2012-2013 season. we also evaluated the impact of the mutations on the ability of ns1 proteins to inhibit host innate immune responses and general gene expression. surprisingly, a previously unidentified muta ...201627535054
cross-reactive antibodies against h7n9 and h5n1 avian influenza viruses in thai population.avian influenza h5n1 and h7n9 viruses have jumped across species from avian to humans and become a threat to public health. not much is known about pre-existing cross-reactive antibodies against these avian viruses in human population.201627543728
prevention and control of seasonal influenza with vaccines.this report updates the 2015-16 recommendations of the advisory committee on immunization practices (acip) regarding the use of seasonal influenza vaccines (grohskopf la, sokolow lz, olsen sj, bresee js, broder kr, karron ra. prevention and control of influenza with vaccines: recommendations of the advisory committee on immunization practices, united states, 2015-16 influenza season. mmwr morb mortal wkly rep 2015;64:818-25). routine annual influenza vaccination is recommended for all persons ag ...201627560619
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
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
seasonal influenza vaccination of children induces humoral and cell-mediated immunity beyond the current season: cross-reactivity with past and future strains.influenza viruses gradually accumulate point mutations, reducing the effectiveness of prior immune protection.201627571905
selection of antigenically advanced variants of seasonal influenza viruses.influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. to establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human h1n1 and h3n2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human h1n1 and h3n2 viruses. we also selected ...201627572841
broad spectrum anti-influenza agents by inhibiting self-association of matrix protein 1.the matrix protein 1 (m1) of influenza a virus (iav) exists as a three-dimensional oligomeric structure in mature virions with high sequence conservation across different iav subtypes, which makes it a potential broad spectrum antiviral target. we hypothesized that impairing self-association of m1 through a small molecule 'wedge', which avidly binds to an m1-m1 interface, would result in a completely new class of anti-influenza agents. to establish this proof-of-principle, we performed virtual s ...201627573445
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
size distribution analysis of influenza virus particles using size exclusion chromatography.size exclusion chromatography is a standard method in quality control of biopharmaceutical proteins. in contrast, vaccine analysis is often based on activity assays. the hemagglutination assay is a widely accepted influenza quantification method, providing no insight in the size distribution of virus particles. capabilities of size exclusion chromatography to complement the hemagglutination assay are investigated. the presented method is comparatively robust regarding different buffer systems, i ...201627578410
virologic differences do not fully explain the diversification of swine influenza viruses in the united states.influenza a(h1n1) viruses entered the u.s. swine population following the 1918 pandemic and remained genetically stable for roughly 80 years. in 1998, there was an outbreak of influenza-like illness among swine that was caused by a(h3n2) viruses containing the triple reassortant internal gene (trig) cassette. following the trig cassette emergence, numerous reassortant viruses were isolated in nature, suggesting that the trig virus had an enhanced ability to reassort compared to the classical swi ...201627581984
m2sr, a novel live single replication influenza virus vaccine, provides effective heterosubtypic protection in mice.despite the annual public health burden of seasonal influenza and the continuing threat of a global pandemic posed by the emergence of highly pathogenic/pandemic strains, conventional influenza vaccines do not provide universal protection, and exhibit suboptimal efficacy rates, even when they are well matched to circulating strains. to address the need for a highly effective universal influenza vaccine, we have developed a novel m2-deficient single replication vaccine virus (m2sr) that induces s ...201627595896
titration of individual strains in trivalent live-attenuated influenza vaccine without neutralization.formulation and quality control of trivalent live-attenuated influenza vaccine requires titration of infectivity of individual strains in the trivalent mix. this is usually performed by selective neutralization of two of the three strains and titration of the un-neutralized strain in cell culture or embryonated eggs. this procedure requires standard sera with high neutralizing titer against each of the three strains. obtaining standard sera, which can specifically neutralize only the correspondi ...201627596269
recommendations for prevention and control of influenza in children, 2016-2017.the purpose of this statement is to update recommendations for the routine use of seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. the aap recommends annual seasonal influenza immunization for everyone 6 months and older, including children and adolescents. highlights for the upcoming 2016-2017 season include the following: 1. annual universal influenza immunization is indicated with either a trivalent or quadrivalent (no preference) ...201627600320
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
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
biochemical and structural characterization of the interface mediating interaction between the influenza a virus non-structural protein-1 and a monoclonal antibody.we have previously shown that a non-structural protein 1 (ns1)-binding monoclonal antibody, termed as 2h6, can significantly reduce influenza a virus (iav) replication when expressed intracellularly. in this study, we further showed that 2h6 binds stronger to the ns1 of h5n1 than a/puerto rico/8/1934(h1n1) because of an amino acid difference at residue 48. a crystal structure of 2h6 fragment antigen-binding (fab) has also been solved and docked onto the ns1 structure to reveal the contacts betwe ...201627633136
influenza in children.in children, influenza is one among the commonest causes of acute respiratory illness and loss of school days. influenza a, b, and c are 3 types of viruses responsible for illness. type a virus has many subtypes based on antigens but type b and type c viruses have no known subtypes. currently, influenza a/h1n1, a/h3n2, and influenza type b viruses are circulating in humans. transmission of influenza occurs through droplets from infected person or through direct contact with person or fomites. cl ...201727641976
reassortment of high-yield influenza viruses in vero cells and safety assessment as candidate vaccine strains.vaccination is the practiced and accessible measure for preventing influenza infection. because chicken embryos used for vaccine production have various insufficiencies, more efficient methods are needed. african green monkey kidney (vero) cells are recommended by the world health organization (who) as a safe substitute for influenza vaccine production for humans. however, the influenza virus usually had low-yield in vero cells, which limits the usage of vero cellular vaccines. this study used 2 ...201727648636
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
update: influenza activity - united states and worldwide, may 22-september 10, 2016.during may 22-september 10, 2016,* the united states experienced typical low levels of seasonal influenza activity overall; beginning in late august, clinical laboratories reported a slight increase in influenza positive test results and cdc received reports of a small number of localized influenza outbreaks caused by influenza a (h3n2) viruses. influenza a (h1n1)pdm09, influenza a (h3n2), and influenza b viruses were detected during may-september in the united states and worldwide. the majority ...201627657671
sensitive detection and simultaneous discrimination of influenza a and b viruses in nasopharyngeal swabs in a single assay using next-generation sequencing-based diagnostics.reassortment of 2009 (h1n1) pandemic influenza virus (pdh1n1) with other strains may produce more virulent and pathogenic forms, detection and their rapid characterization is critical. in this study, we reported a "one-size-fits-all" approach using a next-generation sequencing (ngs) detection platform to extensively identify influenza viral genomes for diagnosis and determination of novel virulence and drug resistance markers. a de novo module and other bioinformatics tools were used to generate ...201727658193
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
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
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
immunity against influenza a(h1n1) infections is determined by age at the time of initial strain circulation.we explored age-dependent patterns in haemagglutination inhibition (hi) titre to seasonal [1956 a(h1n1), 1977 a(h1n1), 2007 a(h1n1)] and pandemic [a(h1n1)pdm09] influenza strains using serological data collected from an adult french influenza cohort. subjects were recruited by their general practitioners from 2008 to 2009 and followed until 2010. we explored age-related differences between strain-specific hi titres using 1053 serological samples collected over the study period from 398 unvaccina ...201727682472
genetic characterization of influenza viruses from influenza-related hospital admissions in the st. petersburg and valencia sites of the global influenza hospital surveillance network during the 2013/14 influenza season.continuous surveillance for genetic changes in circulating influenza viruses is needed to guide influenza prevention and control.201627690141
an early innate response underlies severe influenza-induced exacerbations of asthma in a novel steroid-insensitive and anti-il-5-responsive mouse model.acute worsening of asthma symptoms (exacerbation) is predominantly triggered by respiratory viruses, with influenza causing the most severe exacerbations. the lack of an adequate animal model hampers mechanistic insight and the development of new therapeutics.201727696462
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
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
constitutively expressed ifitm3 protein in human endothelial cells poses an early infection block to human influenza viruses.a role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. as the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. we found that a subset of avian influenza viruses, including potentially pandemic h5n1, h7n9, and h9n2 viruses, could infect huma ...201627707929
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
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
characteristics of severe acute respiratory infectionassociated hospitalization in yemen, 2014/15.this study aims to describe etiological agents, demographic details of patients, seasonality and underlying conditions among patients hospitalized due to viral severe acute respiratory infection (sari) in yemen. we carried out a retrospective descriptive analysis of data from january 2014 to december 2015. nasopharyngeal swabs were taken from each patient for laboratory testing. a total of 1346 diagnostic specimens were tested, of which 733 (54%) were positive for influenza viruses. influenza a( ...201627714737
detection of influenza b viruses with reduced sensitivity to neuraminidase inhibitor in morocco during 2014/15 season.we monitored phenotypic and genotypic susceptibility of influenza viruses circulating in morocco during 2014-2015 to oseltamivir and zanamivir. throat and nasal swab specimens were collected from outpatients (with influenza-like illness) and inpatients (with severe acute respiratory illness) and tested for influenza viruses using real-time reverse transcription polymerase chain reaction. positive samples were inoculated in mdck cells and virus phenotypic susceptibility to neuraminidase inhibitor ...201627714739
modelling of seasonal influenza and estimation of the burden in tunisia.the burden of influenza was estimated from surveillance data in tunisia using epidemiological parameters of transmission with who classical tools and mathematical modelling. the incidence rates of influenza-associated influenza-like illness (ili) per 100 000 were 18 735 in 2012/2013 season; 5536 in 2013/14 and 12 602 in 2014/15. the estimated proportions of influenza-associated ili in the total outpatient load were 3.16%; 0.86% and 1.98% in the 3 seasons respectively. distribution of influenza v ...201627714740
molecular epidemiology and evolution of a(h1n1) pdm09 and h3n2 viruses in jordan, 2011-2013.understanding the genetic evolution of a(h1n1)pdm09 and h3n2 viruses can help better select strains to be included in the annual influenza vaccine. there is little information on their evolution in jordan so this study investigated the genetic and antigenic variability of a(h1n1)pdm09 and h3n2 viruses in jordan by performing phylogenetic and genetic analyses of the ha and na genes of a(h1n1)pdm09 and h3n2 viruses between 2011 and 2013. the full ha and na genes of 16 h1n1-positive samples obtaine ...201627714744
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
characterization of influenza outbreaks in lebanon during the 2013/14 and 2014/15 seasons.despite the significant burden of influenza outbreaks, active disease monitoring has been largely absent in the middle east, including lebanon. in this study we characterized influenza virus in 440 nasopharyngeal swabs collected from patients with acute respiratory infections during two influenza seasons in lebanon. influenza a(h3n2) was dominant in the 2013/14 season while the a(h1n1)pdm09 and b/yamagata strains were most prevalent in the 2014/15 season. all tested isolates were susceptible to ...201627714749
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
virological surveillance of influenza in four recent post-pandemic seasons (2010/11 to 2013/14) in bulgaria.influenza virological surveillance is an essential tool for studying the evolution of influenza viruses as well as for annual updating of the vaccine composition. the aim of the present study is to analyse the circulation of the influenza viruses in bulgaria during the four recent post-pandemic seasons.201627755859
improving influenza virological surveillance in europe: strain-based reporting of antigenic and genetic characterisation data, 11 european countries, influenza season 2013/14.influenza antigenic and genetic characterisation data are crucial for influenza vaccine composition decision making. previously, aggregate data were reported to the european centre for disease prevention and control by european union/european economic area (eu/eea) countries. a system for collecting case-specific influenza antigenic and genetic characterisation data was established for the 2013/14 influenza season. in a pilot study, 11 eu/eea countries reported through the new mechanism. we demo ...201627762211
circulation of multiple genotypes of h1n2 viruses in a swine farm in italy over a two-month period.in august 2012 repeated respiratory outbreaks caused by swine influenza a virus (swiav) were registered for a whole year in a breeding farm in northeast italy that supplied piglets for fattening. the virus, initially characterized in the farm, was a reassortant eurasian avian-like h1n1 (h1avn1) genotype, containing a haemagglutinin segment derived from the pandemic h1n1 (a(h1n1)pdm09) lineage. to control infection, a vaccination program using vaccines against the a(h1n1)pdm09, human-like h1n2 (h ...201627771067
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
in vitro exposure system for study of aerosolized influenza virus.infection of adherent cell monolayers using a liquid inoculum represents an established method to reliably and quantitatively study virus infection, but poorly recapitulates the exposure and infection of cells in the respiratory tract that occurs during infection with aerosolized pathogens. to better simulate natural infection in vitro, we adapted a system that generates viral aerosols similar to those exhaled by infected humans to the inoculation of epithelial cell monolayers. procedures for ce ...201727771560
fatal cases of seasonal influenza in russia in 2015-2016.the influenza epidemic in 2015-2016 in russia is characterized by a sharp increase of influenza cases (beginning from the second week of 2016) with increased fatalities. influenza was confirmed in 20 fatal cases registered among children (0-10 years), in 5 cases among pregnant women, and in 173 cases among elderly people (60 years and older). two hundred and ninety nine people died from influenza were patients with some chronic problems. the overwhelming majority among the deceased (more than 98 ...201627776172
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
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
comparative analysis of influenza a(h3n2) virus hemagglutinin specific igg subclass and iga responses in children and adults after influenza vaccination.two different influenza vaccines are generally used in many countries; trivalent live attenuated influenza vaccine (laiv3) and trivalent inactivated influenza vaccine (iiv3). studies comparing the antibody response to iiv3 and laiv3 commonly investigate the seroprotective response by hemagglutination-inhibition (hi) assay. however, there is limited data regarding comparative analysis of igg subclass and iga responses induced by laiv3 and iiv3. fifteen children <5years received 2 doses of laiv3 w ...201727789145
a pyrosequencing-based approach to high-throughput identification of influenza a(h3n2) virus clades harboring antigenic drift variants.the rapid evolution of influenza a(h3n2) viruses necessitates close monitoring of their antigenic properties so the emergence and spread of antigenic drift variants can be rapidly identified. changes in hemagglutinin (ha) acquired by contemporary a(h3n2) viruses hinder antigenic characterization by traditional methods, thus complicating vaccine strain selection. sequence-based approaches have been used to infer virus antigenicity; however, they are time consuming and mid-throughput. to facilitat ...201727795346
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
serum 25-hydroxyvitamin d was not associated with influenza virus infection in children and adults in hong kong, 2009-2010.some studies have hypothesized that vitamin d may have a role to play in protection against influenza virus infections and illnesses, and that seasonal fluctuation in serum 25-hydroxyvitamin d [25(oh)d] may affect seasonal patterns of influenza virus infections.201627798334
exogenous activation of invariant natural killer t cells by α-galactosylceramide reduces pneumococcal outgrowth and dissemination postinfluenza.influenza a virus infection can predispose to potentially devastating secondary bacterial infections. invariant natural killer t (inkt) cells are unconventional, lipid-reactive t lymphocytes that exert potent immunostimulatory functions. using a mouse model of postinfluenza invasive secondary pneumococcal infection, we sought to establish whether α-galactosylceramide (α-galcer [a potent inkt cell agonist that is currently in clinical development]) could limit bacterial superinfection. our result ...201627803187
amino acids in hemagglutinin antigenic site b determine antigenic and receptor binding differences between a(h3n2)v and ancestral seasonal h3n2 influenza viruses.influenza a h3n2 variant [a(h3n2)v] viruses, which have caused human infections in the united states in recent years, originated from human seasonal h3n2 viruses that were introduced into north american swine in the mid-1990s, but they are antigenically distinct from both the ancestral and current circulating h3n2 strains. a reference a(h3n2)v virus, a/minnesota/11/2010 (mn/10), and a seasonal h3n2 strain, a/beijing/32/1992 (bj/92), were chosen to determine the molecular basis for the antigenic ...201727807224
a promising magnetic sers immunosensor for sensitive detection of avian influenza virus.avian influenza viruses infect a great number of global populations every year and can lead to severe epidemics with high morbidity and mortality. facile, rapid and sensitive detection of viruses is very crucial to control the viral spread at its early stage. in this work, we developed a novel magnetic immunosensor based on surface enhanced raman scattering (sers) spectroscopy to detect intact but inactivated influenza virus h3n2 (a/shanghai/4084t/2012) by constructing a sandwich complex consist ...201727818055
molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination.molecular understanding of serological immunity to influenza has been confounded by the complexity of the polyclonal antibody response in humans. here we used high-resolution proteomics analysis of immunoglobulin (referred to as ig-seq) coupled with high-throughput sequencing of transcripts encoding b cell receptors (bcr-seq) to quantitatively determine the antibody repertoire at the individual clonotype level in the sera of young adults before and after vaccination with trivalent seasonal influ ...201627820605
influence of social contact patterns and demographic factors on influenza simulation results.the demographic composition and the frequency and nature of social contacts may affect the spread of influenza virus in a population, resulting in distinct age-dependent immunity patterns. as demography and social contact rates differ strongly between european countries, this may impact infection incidence and vaccine effectiveness and thus limit the extent to which conclusions derived from observations in one country can be generalized to others. in the current study, we aimed to decipher the i ...201627821137
genotyping and detection of common avian and human origin-influenza viruses using a portable chemiluminescence imaging microarray.influenza viruses are divided into three types, a, b, and c. human influenza a and b viruses can cause seasonal epidemics, but influenza c causes only a mild respiratory illness. influenza a virus can infect various host species. in 2013, human-infectious avian influenza a (h7n9) was first reported in china. by the second week of 2014, there were 210 laboratory-confirmed human cases in the country, and the mortality rate eventually reached 22 %. rapid and accurate diagnosis of influenza viruses ...201627822445
versatility of a localized surface plasmon resonance-based gold nanoparticle-alloyed quantum dot nanobiosensor for immunofluorescence detection of viruses.flu infection, caused by the influenza virus, constitutes a serious threat to human lives worldwide. a rapid, sensitive and specific diagnosis is urgently needed for point-of-care treatment and to control the rapid spread of this disease. in this study, an ultrasensitive, rapid and specific localized surface plasmon resonance (lspr)-induced immunofluorescence nanobiosensor has been developed for the influenza virus based on a gold nanoparticle (aunp)-induced quantum dot (qd) fluorescence signal. ...201727825520
high antiviral effect of tio2·pl-dna nanocomposites targeted to conservative regions of (-)rna and (+)rna of influenza a virus in cell culture.background: the development of new antiviral drugs based on nucleic acids is under scrutiny. an important problem in this aspect is to find the most vulnerable conservative regions in the viral genome as targets for the action of these agents. another challenge is the development of an efficient system for their delivery into cells. to solve this problem, we proposed a tio2·pl-dna nanocomposite consisting of titanium dioxide nanoparticles and polylysine (pl)-containing oligonucleotides. results: ...201627826491
seasonal influenza a h1n1pdm09 virus and severe outcomes: a reason for broader vaccination in non-elderly, at-risk people.recent pandemics of influenza a h1n1pdm09 virus have caused severe illness, especially in young people. very few studies on influenza a h1n1pdm09 in post-pandemic periods exist, and there is no information on the severity of both seasonal influenza a(h1n1) and a(h3n2) from the same season, adjusting for potential confounders, including vaccine.201627832114
surveillance of antiviral resistance markers in argentina: detection of e119v neuraminidase mutation in a post-treatment immunocompromised patient.although vaccines are the best means of protection against influenza, neuraminidase inhibitors are currently the main antiviral treatment available to control severe influenza cases. one of the most frequent substitutions in the neuraminidase (na) protein of influenza a(h3n2) viruses during or soon after oseltamivir administration is e119v mutation. we describe the emergence of a mixed viral population with the e119e/v mutation in the na protein sequence in a post-treatment influenza sample coll ...201627849220
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
origin, distribution, and potential risk factors associated with influenza a virus in swine in two production systems in guatemala.guatemala is the country with the largest swine production in central america; however, evidence of influenza a virus (iav) in pigs has not been clearly delineated.201727860313
identification of inonotus obliquus polysaccharide with broad-spectrum antiviral activity against multi-feline viruses.inonotus obliquus polysaccharides (iops) are a potential drug for the prevention and treatment of cancer, cardiopathy, diabetes, aids, pancreatitis and other diseases. in this study, we found that iop can act as a broad-spectrum antiviral drug against feline viruses in the in vitro experiment. using cell models of feline calicivirus (fcv), we demonstrated that iop treatment was capable of exhibiting anti-fcv strain f9 activity in cell-based assays and also showed low cytotoxicity. investigation ...201727865960
influenza h7n9 lah-hbc virus-like particle vaccine with adjuvant protects mice against homologous and heterologous influenza viruses.the long alpha-helix (lah) region located in influenza virus hemagglutinin (ha) shows conservation among different influenza a strains, which could be used as a candidate target of influenza vaccines. moreover, the hepatitis b virus core protein (hbc) is a carrier for heterologous epitopes in eliciting effective immune responses. we inserted the lah region of h7n9 influenza virus into the hbc and prepared the lah-hbc protein, which were capable of self-assembly into virus-like particles (vlp), b ...201627866773
monitoring respiratory virus infection in the metropolitan area of belo horizonte, brazil, 2011-2013.to analyze the circulation of respiratory viruses in people living in the metropolitan area of belo horizonte, brazil, and hospitalized in belo horizonte from 2011 to 2013.201627869941
influenza in poland in 2013 and 2013/2014 epidemic seasonanalysis of epidemiological situation of influenza in poland in 2013 and 2013/14 epidemic season in reference to previous years and seasons.201727883286
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
school absenteeism among school-aged children with medically attended acute viral respiratory illness during three influenza seasons, 2012-2013 through 2014-2015.acute respiratory illnesses (aris) are common in school-aged children, but few studies have assessed school absenteeism due to specific respiratory viruses.201627885805
influenza and rhinovirus viral load and disease severity in upper respiratory tract infections.the role of viral load in respiratory viral infection is unclear. it is proposed that the viral load of some, but not all respiratory viruses correlate with disease severity.201727893998
virospot microneutralization assay for antigenic characterization of human influenza viruses.the hemagglutination inhibition (hi) assay has been used for the antigenic characterization of influenza viruses for decades. however, the majority of recent seasonal influenza a viruses of the h3n2 subtype has lost the capacity to agglutinate erythrocytes of various species. the hemagglutination (ha) activity of other a(h3n2) strains is generally sensitive to the action of the neuraminidase inhibitor oseltamivir, which indicates that the neuraminidase and not the hemagglutinin is responsible fo ...201727899226
establishment of memory cd8+ t cells with live attenuated influenza virus across different vaccination doses.flumist has been used in children and adults for more than 10 years. as pre-existing cd8+ t cell memory pools can provide heterologous immunity against distinct influenza viruses, it is important to understand influenza-specific cd8+ t cell responses elicited by different live attenuated influenza virus (laiv) regimens. in this study, we immunized mice intranasally with two different doses of live-attenuated pr8 virus (pr8 ts, h1n1), low and high, and then assessed protective efficacy by challen ...201627902386
performance evaluation of allplex respiratory panels 1, 2, and 3 for detection of respiratory viruses and influenza a virus subtypes.the allplex respiratory panels 1, 2, and 3 (allplex) comprise a one-step real-time reverse transcription-pcr assay for the detection of respiratory viruses (rvs) and influenza a subtypes based on multiple detection temperature (mudt) technology. the performance of the allplex assay was compared with those of the advansure rv real-time pcr kit (advansure) and the powerchek pandemic h1n1/h3n2/h5n1 real-time pcr kit (powerchek) using 417 clinical respiratory specimens. in comparison with the advans ...201727903601
effect of seasonal vaccination on the selection of influenza a/h3n2 epidemic variants.the effect of vaccination on the dynamics of influenza virus variants remains largely unknown in humans, unlike in poultry. in this study, we compared influenza hemagglutinin (ha) gene sequences isolated from vaccinated and unvaccinated populations with the yearly vaccine strains. in total, 181 influenza a/h3n2 virus samples isolated from 82 vaccinated and 99 unvaccinated patients (2011-15, four japanese influenza seasons) were genetically analyzed using a next-generation sequencer. amino acid ( ...201727919631
influenza a virus vaccines for swine.economic losses due to influenza a virus (iav) infections are substantial and a global problem, ranking among the top three major health challenges in the swine industry. currently, h1 and h3 subtypes circulate in pigs globally associated with different combinations of n1 and n2 subtypes; however, the origin, gene constellation, and antigenic makeup of iav vary greatly on different continents. vaccination is one means of mitigating the effects of iav disease, and vaccines are most effective if t ...201627923501
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
reassortment between swine h3n2 and 2009 pandemic h1n1 in the united states resulted in influenza a viruses with diverse genetic constellations with variable virulence in pigs.repeated spillovers of the h1n1 pandemic virus (h1n1pdm09) from humans to pigs resulted in substantial evolution of influenza a viruses infecting swine, contributing to the genetic and antigenic diversity of influenza a viruses (iav) currently circulating in swine. the reassortment with endemic swine viruses and maintenance of some of the h1n1pdm09 internal genes resulted in the circulation of different genomic constellations in pigs. here, we performed a whole-genome phylogenetic analysis of 36 ...201727928015
temperature-sensitive live-attenuated canine influenza virus h3n8 vaccine.canine influenza is a respiratory disease of dogs caused by canine influenza virus (civ). civ subtypes responsible for influenza in dogs include h3n8, which originated from the transfer of h3n8 equine influenza virus to dogs; and the h3n2 civ, which is an avian-origin virus that adapted to infect dogs. influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. currently, only inactivated influenza vaccines (iivs) are available for the pre ...201727928017
influenza not mers cov among returning hajj and umrah pilgrims with respiratory illness, kashmir, north india, 2014-15.the increasing reports of middle east respiratory syndrome (mers) caused by mers coronavirus (mers-cov) from many countries emphasize its importance for international travel. muslim pilgrimages of hajj and umrah involve mass gatherings of international travellers. we set out to assess the presence of influenza and mers-cov in hajj/umrah returnees with acute respiratory infection. .201727932291
generation and characterisation of monoclonal antibodies specific to avian influenza h7n9 haemagglutinin protein.emerging virulent strains of influenza virus pose a serious public health threat with potential pandemic consequences. a novel avian influenza virus, h7n9, breached the species barrier from infected domestic poultry to humans in 2013 in china. since then, it has caused numerous infections in humans with a close contact to poultry.201727934828
epidemiological and virological characteristics of influenza in chongqing, china, 2011-2015.chongqing is the largest municipality and located in southwestern of china, with over 30 million registered inhabitants. there are few reports regarding the epidemiology of influenza in chongqing. the objective of the paper is to explore the epidemiology of influenza in chongqing, in order to provide scientific basis for prevention and control of influenza.201627936139
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
in vitro anti-viral activity of psoraleae semen water extract against influenza a viruses.influenza causes respiratory infections and poses health risks to humans and animals; its effects are complicated by increasing resistance to existing anti-influenza viral agents. therefore, novel therapeutic approaches against influenza virus infection are required. psoraleae semen has been widely used in traditional medicine in korea, taiwan, china, and japan for treating and preventing various diseases. in this study, we examined the anti-viral activities and mechanism of action of the water ...201627965579
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