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a novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses.a safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. in light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, p9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza a virus h1n1, h3n2, h5n1, h7n7, h7n9, sars-cov and mers-cov. the antiviral activity of p9 w ...201626911565
influenza b vaccine lineage selection--an optimized trivalent vaccine.epidemics of seasonal influenza viruses cause considerable morbidity and mortality each year. various types and subtypes of influenza circulate in humans and evolve continuously such that individuals at risk of serious complications need to be vaccinated annually to keep protection up to date with circulating viruses. the influenza vaccine in most parts of the world is a trivalent vaccine, including an antigenically representative virus of recently circulating influenza a/h3n2, a/h1n1, and influ ...201626896685
update: influenza activity--united states, october 4, 2015-february 6, 2016.from october through mid-december 2015, influenza activity remained low in most regions of the united states. activity began to increase in late december 2015 and continued to increase slowly through early february 2016. influenza a viruses have been most frequently identified, with influenza a (h3n2) viruses predominating during october until early december, and influenza a (h1n1)pdm09 viruses predominating from mid-december until early february. most of the influenza viruses characterized duri ...201626891596
the proteolytic activation of (h3n2) influenza a virus hemagglutinin is facilitated by different type ii transmembrane serine proteases.cleavage of influenza virus hemagglutinin (ha) by host cell proteases is necessary for viral activation and infectivity. in humans and mice, members of the type ii transmembrane protease family (ttsp), e.g., tmprss2, tmprss4, and tmprss11d (hat), have been shown to cleave influenza virus ha for viral activation and infectivity in vitro recently, we reported that inactivation of a single ha-activating protease gene,tmprss2, in knockout mice inhibits the spread of h1n1 influenza viruses. however, ...201626889029
airborne influenza a is detected in the personal breathing zone of swine veterinarians.the 2009 h1n1 pandemic emphasized a need to evaluate zoonotic transmission of influenza a in swine production. airborne influenza a virus has been detected in swine facilities during an outbreak. however, the personal exposure of veterinarians treating infected swine has not been characterized. two personal bioaerosol samplers, the niosh bioaerosol sampler and the personal high-flow inhalable sampler head (phish), were placed in the breathing zone of veterinarians treating swine infected with ei ...201626867129
long-term shedding of influenza virus, parainfluenza virus, respiratory syncytial virus and nosocomial epidemiology in patients with hematological disorders.respiratory viruses are a cause of upper respiratory tract infections (urti), but can be associated with severe lower respiratory tract infections (lrti) in immunocompromised patients. the objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (rsv) and the duration of viral shedding in hematological patients. nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and rsv on a ...201626866481
effectiveness of subunit influenza vaccination in the 2014-2015 season and residual effect of split vaccination in previous seasons.in navarra, spain, subunit vaccine was first used in the 2014-2015 season, whereas trivalent split-virion influenza vaccines had been used in previous seasons. we estimate the effectiveness of the subunit vaccine in the current season and split vaccine in the two previous seasons against laboratory-confirmed influenza in the 2014-2015 season.201626854911
a natural component from euphorbia humifusa willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein.the need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. we identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-o-galloyl-β-d-glucopyranoside (tgbg) from euphorbia humifusa willd showed broad-spectrum anti-influenza activity ...201626850850
predicting the mutating distribution at antigenic sites of the influenza virus.mutations of the influenza virus lead to antigenic changes that cause recurrent epidemics and vaccine resistance. preventive measures would benefit greatly from the ability to predict the potential distribution of new antigenic sites in future strains. by leveraging the extensive historical records of ha sequences for 90 years, we designed a computational model to simulate the dynamic evolution of antigenic sites in a/h1n1. with templates of antigenic sequences, the model can effectively predict ...201626837263
recombinant influenza virus expressing hiv-1 p24 capsid protein induces mucosal hiv-specific cd8 t-cell responses.influenza viruses are promising mucosal vaccine vectors for hiv but their use has been limited by difficulties in engineering the expression of large amounts of foreign protein. we developed recombinant influenza viruses incorporating the hiv-1 p24 gag capsid into the ns-segment of pr8 (h1n1) and x31 (h3n2) influenza viruses with the use of multiple 2a ribosomal skip sequences. despite the insertion of a sizable hiv-1 gene into the influenza genome, recombinant viruses were readily rescued to hi ...201626826545
construction of the influenza a virus transmission tree in a college-based population: co-transmission and interactions between influenza a viruses.co-infection of different influenza a viruses is known to occur but how viruses interact within co-infection remains unknown. an outbreak in a college campus during the 2009 pandemic involved two subtypes of influenza a: persons infected with pandemic a/h1n1; persons infected with seasonal a/h3n2 viruses; and persons infected with both at the same time (co-infection). this provides data to analyse the possible interaction between influenza a viruses within co-infection.201626825326
molecular characteristics of influenza virus type b lineages circulating in poland.from the time of the hong kong pandemic of 1968-1969, vaccines against influenza are trivalent, containing two subtypes of influenza type a: a/h1n1/ and a/h3n2/, and influenza type b. in 1980, circulation of the new yamagata and victoria lineages of influenza b virus was noted. since both lineages have continued to circulate, the second lineage of influenza b was included into the trivalent vaccine as of the 2013/2014 epidemic season. in poland, co-circulation of influenza type a and b has been ...201626820730
antiviral activity of sa-2 against influenza a virus in vitro/vivo and its inhibition of rna polymerase.a target-free and cell-based approach was applied to evaluate the anti-influenza properties of six newly synthesized benzoic acid derivatives. sa-2, the ethyl 4-(2-hydroxymethyl-5-oxopyrrolidin-1-yl)-3-[3-(3-methylbenzoyl)-thioureido] benzoate (compound 2) was screened as a potential drug candidate. in a cytopathic effect assay, sa-2 dose dependently inhibited h1n1, h3n2 and the oseltamivir-resistant mutant h1n1-h275y influenza viruses in both virus-infected mdck and a549 cells, with 50% effecti ...201626802558
design, synthesis, and in vitro biological evaluation of novel 6-methyl-7-substituted-7-deaza purine nucleoside analogs as anti-influenza a agents.among many subtypes of influenza a viruses, influenza a(h1n1) and a(h3n2) subtypes are currently circulating among humans (who report 2014-15). therapeutically, the emergence of viral resistance to currently available drugs (adamantanes and neuraminidase inhibitors) has heightened alarms for developing novel drugs that could address diverse targets in the viral replication cycle in order to improve treatment outcomes. to this regard, the design and synthesis of nucleoside analog inhibitors as po ...201626802557
an individualized predictor of health and disease using paired reference and target samples.consider the problem of designing a panel of complex biomarkers to predict a patient's health or disease state when one can pair his or her current test sample, called a target sample, with the patient's previously acquired healthy sample, called a reference sample. as contrasted to a population averaged reference this reference sample is individualized. automated predictor algorithms that compare and contrast the paired samples to each other could result in a new generation of test panels that ...201626801061
platform technology to generate broadly cross-reactive antibodies to α-helical epitopes in hemagglutinin proteins from influenza a viruses.we have utilized a de novo designed two-stranded α-helical coiled-coil template to display conserved α-helical epitopes from the stem region of hemagglutinin (ha) glycoproteins of influenza a. the immunogens have all the surface-exposed residues of the native α-helix in the native ha protein of interest displayed on the surface of the two-stranded α-helical coiled-coil template. this template when used as an immunogen elicits polyclonal antibodies which bind to the α-helix in the native protein. ...201626799790
discovery of influenza a virus sequence pairs and their combinations for simultaneous heterosubtypic targeting that hedge against antiviral resistance.the multiple circulating human influenza a virus subtypes coupled with the perpetual genomic mutations and segment reassortment events challenge the development of effective therapeutics. the capacity to drug most rnas motivates the investigation on viral rna targets. 123,060 segment sequences from 35,938 strains of the most prevalent subtypes also infecting humans-h1n1, 2009 pandemic h1n1, h3n2, h5n1 and h7n9, were used to identify 1,183 conserved rna target sequences (≥15-mer) in the internal ...201626771381
influenza in the emergency department: vaccination, diagnosis, and treatment: clinical practice paper approved by american academy of emergency medicine clinical guidelines committee.influenza is an acute respiratory virus that results in significant worldwide morbidity and mortality each year. as emergency physicians, we are often the first to encounter patients with seasonal influenza. it is therefore critical that we draw on the most recent and relevant research when we make clinical decisions regarding the diagnosis, treatment, and prophylaxis of this disease.201626763858
accelerating influenza research: vaccines, antivirals, immunomodulators and monoclonal antibodies. the manufacture of a new wild-type h3n2 virus for the human viral challenge model.influenza and its associated diseases are a major cause of morbidity and mortality. the united states advisory committee on immunization practices recommends influenza vaccination for everyone over 6 months of age. the failure of the flu vaccine in 2014-2015 demonstrates the need for a model that allows the rapid development of novel antivirals, universal/intra-seasonal vaccines, immunomodulators, monoclonal antibodies and other novel treatments. to this end we manufactured a new h3n2 influenza ...201626761707
characterization of viral load, viability and persistence of influenza a virus in air and on surfaces of swine production facilities.indirect transmission of influenza a virus (iav) in swine is poorly understood and information is lacking on levels of environmental exposure encountered by swine and people during outbreaks of iav in swine barns. we characterized viral load, viability and persistence of iav in air and on surfaces during outbreaks in swine barns. iav was detected in pigs, air and surfaces from five confirmed outbreaks with 48% (47/98) of oral fluid, 38% (32/84) of pen railing and 43% (35/82) of indoor air sample ...201626757362
are plasma mineral levels related to antibody response to influenza vaccination in older adults?an effective immune response to vaccination may be related to nutritional status. this study examined the association of plasma mineral levels with hemagglutination inhibition (hi) titers produced in response to influenza vaccine in older adults.201626751915
prevalence of influenza a virus in exhibition swine during arrival at agricultural fairs.the exhibition swine at agricultural fairs provides a critical human-swine interface that allows for the bidirectional transmission of influenza a virus (iav). previous iav surveillance at the end of fairs has resulted in frequent detection of iav-infected swine; little is known, however, about the frequency with which swine arrive at fairs already infected with iav. we investigated the iav prevalence among exhibition swine entering fairs to better understand the epidemiology of iav in this uniq ...201626750204
epidemiology of hospital admissions with influenza during the 2013/2014 northern hemisphere influenza season: results from the global influenza hospital surveillance network.the global influenza hospital surveillance network was established in 2012 to obtain valid epidemiologic data on hospital admissions with influenza-like illness. here we describe the epidemiology of admissions with influenza within the northern hemisphere sites during the 2013/2014 influenza season, identify risk factors for severe outcomes and complications, and assess the impact of different influenza viruses on clinically relevant outcomes in at-risk populations.201627196667
microrna regulation of human genes essential for influenza a (h7n9) replication.influenza a viruses are important pathogens of humans and animals. while seasonal influenza viruses infect humans every year, occasionally animal-origin viruses emerge to cause pandemics with significantly higher morbidity and mortality rates. in march 2013, the public health authorities of china reported three cases of laboratory confirmed human infection with avian influenza a (h7n9) virus, and subsequently there have been many cases reported across south east asia and recently in north americ ...201627166678
influenza vaccine effectiveness in italy: age, subtype-specific and vaccine type estimates 2014/15 season.the 2014/15 influenza season in europe was characterised by the circulation of influenza a(h3n2) viruses with an antigenic and genetic mismatch from the vaccine strain a/texas/50/2012(h3n2) recommended for the northern hemisphere for the 2014/15 season. italy, differently from other eu countries where most of the subtyped influenza a viruses were h3n2, experienced a 2014/15 season characterized by an extended circulation of two influenza viruses: a(h1n1)pdm09 and a(h3n2), that both contributed s ...201627154392
detection and typing of human-infecting influenza viruses in china by using a multiplex dna biochip assay.rapid identification of the infections of specific subtypes of influenza viruses is critical for patient treatment and pandemic control. here we report the application of multiplex reverse transcription polymerase chain reaction (rt-pcr) coupled with membrane-based dna biochip to the detection and discrimination of the type (a and b) and subtype (human h1n1, human h3n2, avian h5n1 and avian h7n9) of influenza viruses in circulation in china. a multiplex one-step rt-pcr assay was designed to simu ...201627150046
analysis of the beta-propiolactone sensitivity and optimization of inactivation methods for human influenza h3n2 virus.beta-propiolactone (bpl) is used as an inactivating reagent for influenza virus in a number of countries. however, the treatment of viruses with bpl occasionally results in a decrease in the hemagglutinin (ha) titer, which complicates vaccine development. in the present study, we examined the biological and biochemical characteristics of human h1n1 and h3n2 viruses treated with bpl, and developed an inactivation method for bpl-sensitive viruses. a significant decrease in ha titer was detected in ...201627142111
virulence of a novel reassortant canine h3n2 influenza virus in ferret, dog and mouse models.an outbreak of a canine influenza virus (civ) h3n2 reassortant derived from pandemic (pdm) h1n1 and civ h3n2 in companion animals has underscored the urgent need to monitor civ infections for potential zoonotic transmission of influenza viruses to humans. in this study, we assessed the virulence of a novel civ h3n2 reassortant, vc378, which was obtained from a dog that was coinfected with pdm h1n1 and civ h3n2, in ferrets, dogs, and mice. significantly enhanced virulence of vc378 was demonstrate ...201627138550
virological characteristics of the 2014/2015 influenza season based on molecular analysis of biological material derived from i-move study.the main goal of the international study i-move (influenza monitoring of vaccine effectiveness) implemented in poland is to identify and evaluate the activity types of influenza virus and to determine the effectiveness of vaccination against influenza in the 2014-2015 influenza season. the study is based on selecting patients with flu symptoms and collecting biological samples for laboratory examination. detection, typing, and subtyping of influenza viruses were carried out by the national cente ...201627131497
concordance of interim and final estimates of influenza vaccine effectiveness: a systematic review.the world health organization's global influenza surveillance and response system meets twice a year to generate a recommendation for the composition of the seasonal influenza vaccine. interim vaccine effectiveness (ve) estimates provide a preliminary indication of influenza vaccine performance during the season and may be useful for decision making. we reviewed 17 pairs of studies reporting 33 pairs of interim and final estimates using the test-negative design to evaluate whether interim estima ...201627124573
i-move multicentre case-control study 2010/11 to 2014/15: is there within-season waning of influenza type/subtype vaccine effectiveness with increasing time since vaccination?since the 2008/9 influenza season, the i-move multicentre case-control study measures influenza vaccine effectiveness (ve) against medically-attended influenza-like-illness (ili) laboratory confirmed as influenza. in 2011/12, european studies reported a decline in ve against influenza a(h3n2) within the season. using combined i-move data from 2010/11 to 2014/15 we studied the effects of time since vaccination on influenza type/subtype-specific ve. we modelled influenza type/subtype-specific ve b ...201627124420
pandemic vaccination strategies and influenza severe outcomes during the influenza a(h1n1)pdm09 pandemic and the post-pandemic influenza season: the nordic experience.during the 2009/10 influenza a(h1n1)pdm09 pandemic, the five nordic countries adopted different approaches to pandemic vaccination. we compared pandemic vaccination strategies and severe influenza outcomes, in seasons 2009/10 and 2010/11 in these countries with similar influenza surveillance systems. we calculated the cumulative pandemic vaccination coverage in 2009/10 and cumulative incidence rates of laboratory confirmed a(h1n1)pdm09 infections, intensive care unit (icu) admissions and deaths ...201627123691
antigen nature and complexity influence human antibody light chain usage and specificity.human antibodies consist of a heavy chain and one of two possible light chains, kappa (κ) or lambda (λ). here we tested how these two possible light chains influence the overall antibody response to polysaccharide and protein antigens by measuring light chain usage in human monoclonal antibodies from antibody secreting cells obtained following vaccination with pneumovax23. remarkably, we found that individuals displayed restricted light chain usage to certain serotypes and that lambda antibodies ...201627113164
a point mutation in the polymerase protein pb2 allows a reassortant h9n2 influenza isolate of wild-bird origin to replicate in human cells.h9n2 influenza a viruses are on the list of potentially pandemic subtypes. therefore, it is important to understand how genomic reassortment and genetic polymorphisms affect phenotypes of h9n2 viruses circulating in the wild bird reservoir. a comparative genetic analysis of north american h9n2 isolates of wild bird origin identified a naturally occurring reassortant virus containing gene segments derived from both north american and eurasian lineage ancestors. the pb2 segment of this virus encod ...201627101787
construction high-yield candidate influenza vaccine viruses in vero cells by reassortment.usage of influenza vaccine is the best choice measure for preventing and conclusion of influenza virus infection. although it has been used of chicken embryo to produce influenza vaccine, following with who recommended vaccine strain, there were uncontrollable factors and its deficiencies, specially, during an influenza pandemic in the world. the vero cells are used for vaccine production of a few strains including influenza virus, because of its homology with human, recommended by who. however, ...201627101353
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
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
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
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
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
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
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
hemagglutinin of influenza a virus binds specifically to cell surface nucleolin and plays a role in virus internalization.the hemagglutinin (ha) protein of influenza a virus initiates cell entry by binding to sialic acids on target cells. in the current study, we demonstrated that in addition to sialic acids, influenza a/puerto rico/8/34 h1n1 (pr8) virus ha specifically binds to cell surface nucleolin (ncl). the interaction between ha and ncl was initially revealed with virus overlay protein binding assay (vopba) and subsequently verified with co-immunoprecipitation. importantly, inhibiting cell surface ncl with nc ...201627085069
bioinformatics studies of influenza a hemagglutinin sequence data indicate recombination-like events leading to segment exchanges.the influenza genome is highly variable due primarily to two mechanisms: antigenic drift and antigenic shift. a third mechanism for genetic change, known as copy choice or template switching, can arise during replication when, if two viral strains infect a cell, a part of a gene from the second viral strain can be copied into the growing progeny of a gene of the first viral strain as replacement leading to a new variety of the virus. this template switching between the same genes of the two stra ...201627083561
long-lasting cross-protection against influenza a by neuraminidase and m2e-based immunization strategies.there is mounting evidence that in the absence of neutralizing antibodies cross-reactive t cells provide protection against pandemic influenza viruses. here, we compared protection and cd8+ t cell responses following challenge with h1n1 2009 pandemic and h3n2 viruses of mice that had been immunized with hemagglutinin (ha), neuraminidase (na) and the extracellular domain of matrix protein 2 (m2e) fused to a virus-like particle (vlp). mice were challenged a first time with a sublethal dose of h1n1 ...201627072615
moderate influenza vaccine effectiveness against hospitalisation with a(h3n2) and a(h1n1) influenza in 2013-14: results from the innhove network.we conducted a multicentre test negative case control study to estimate the 2013-14 influenza vaccine effectiveness (ive) against hospitalised laboratory confirmed influenza in 12 hospitals in france, italy and spain. we included all ≥18 years hospitalised patients targeted by local influenza vaccination campaign reporting an influenza-like illness within 7 days before admission. we defined as cases patients rt-pcr positive for influenza and as controls those negative for all influenza virus. we ...201627065000
protective immunity against homologous and heterologous influenza virus lethal challenge by immunization with new recombinant chimeric ha2-m2e fusion protein in balb/c mice.influenza is an acute and highly contagious respiratory disease. the error prone rna polymerase and segmented nature of the influenza a virus genome allow antigenic drift and shift, respectively. therefore, most influenza vaccines are inefficient along time and against different viral subtypes. in this study, for the first time, protection properties of a new recombinant fusion of ha2 and m2e peptides originated from influenza virus a/brisbane/59/2007-like (h1n1) in balb/c mice model were invest ...201627058011
influenza neuraminidase subtype n1: immunobiological properties and functional assays for specific antibody response.influenza neuraminidase (na) proteins expressed in tk- cells infected with recombinant vaccinia virus carrying na gene of highly pathogenic avian influenza h5n1 virus or 2009 pandemic h1n1 (h1n1pdm) virus were characterized for their biological properties, i.e., cell localization, molecular weight (mw), glycosylation and sialidase activity. immune sera collected from balb/c mice immunized with these recombinant viruses were assayed for binding and functional activities of anti-na antibodies. rec ...201627054879
a novel m2e-multiple antigenic peptide providing heterologous protection in mice.swine influenza viruses (swivs) cause considerable morbidity and mortality in domestic pigs, resulting in a significant economic burden. moreover, pigs have been considered to be a possible mixing vessel in which novel strains loom. here, we developed and evaluated a novel m2e-multiple antigenic peptide (m2e-map) as a supplemental antigen for inactivated h3n2 vaccine to provide cross-protection against two main subtypes of swivs, h1n1 and h3n2. the novel tetra-branched map was constructed by fus ...201627051342
influenza a virus and influenza b virus can induce apoptosis via intrinsic or extrinsic pathways and also via nf-κb in a time and dose dependent manner.influenza viruses are able to cause annual epidemics and pandemics due to their mutation rates and reassortment capabilities leading to antigenic shifts and drifts. to identify host response to influenza a and b viruses on a549 and mdck ii cells at low and high mois, expressions of mxa and caspases 3, 8, and 9 and bad, tnfα, and iκbα genes were measured in the cells supernatants. h1n1 and h3n2 prefer to initially enhance the intrinsic pathway, determined by higher caspase 9 activity in mdck ii c ...201627042352
clinical and radiographic comparison of influenza virus-associated pneumonia among three viral subtypes.presently, the predominant subtypes of influenza viruses in the world, except for those in local epidemics, include influenza pandemic h1n1 2009 (ph1n1), h3n2, and b viruses. there are few reports on the differences in the clinical features, radiographic findings, treatment, and outcomes of influenza virus-associated pneumonia among these three viral subtypes. the purpose of this study was to investigate whether the clinical features, radiographic findings, treatment, and outcomes differ among t ...201627041156
the dod global, laboratory-based, influenza surveillance program: summary for the 2013-2014 influenza season.this report for the 2013-2014 influenza season summarizes the results of influenza surveillance carried out by the dod global, laboratory-based, influenza surveillance program, which is managed by the u.s. air force school of aerospace medicine epidemiology consult service and epidemiology laboratory at wright-patterson air force base, oh. sentinel sites submitted 3,903 specimens for clinical diagnostic testing and 1,163 (29.8%) were positive for influenza virus. the predominant influenza subtyp ...201627030925
age at vaccination and timing of infection do not alter vaccine-associated enhanced respiratory disease in influenza a virus-infected pigs.whole inactivated virus (wiv) vaccines are widely used in the swine industry to reduce clinical disease against homologous influenza a virus (iav) infection. in pigs experimentally challenged with antigenically distinct heterologous iav of the same hemagglutinin subtype, wiv vaccinates have been shown to develop vaccine-associated enhanced respiratory disease (vaerd). we evaluated the impact of vaccine valency, age at vaccination, and duration between vaccination and challenge on the development ...201627030585
post-pandemic seroprevalence of human influenza viruses in domestic cats.the continuous exposure of cats to diverse influenza viruses raises the concern of a potential role of cats in the epidemiology of these viruses. our previous seroprevalence study of domestic cat sera collected during the 2009 h1n1 pandemic wave (september 2009-september 2010) revealed a high prevalence of pandemic h1n1, as well as seasonal h1n1 and h3n2 human flu virus infection (22.5%, 33.0%, and 43.5%, respectively). in this study, we extended the serosurvey of influenza viruses in cat sera c ...201627030198
quantifying homologous and heterologous antibody titre rises after influenza virus infection.most influenza virus infections are associated with mild disease. one approach to estimate the occurrence of influenza virus infections in individuals is via repeated measurement of humoral antibody titres. we used baseline and convalescent antibody titres measured by haemagglutination inhibition (hi) and viral neutralization (vn) assays against influenza a(h1n1), a(h3n2) and b viruses to investigate the characteristics of antibody rises following virologically confirmed influenza virus infectio ...201627018720
detection of influenza virus using peroxidase-mimic of gold nanoparticles.a modified enzyme-linked immunosorbent assay (elisa) with nanomaterials is an effective and powerful method to amplify the signal and reduce the cost of detecting and measuring trace biomarkers or proteins. in this study, an ultra-sensitive colorimetric immunoassay was designed, and its ability to detect influenza viruses using positively charged gold nanoparticles ((+)au nps) was assessed as a possible role for peroxidase-mimic inorganic enzymes. this method detected influenza virus a (h1n1) wi ...201627002303
viral infections in children in the 2014/2015 epidemic season in poland.in every epidemic season, viral infections affect the general population, including children, which is an underestimated issue. the present study demonstrates the results of examination of 802 clinical samples obtained from pediatric patients aged 0-14 years during the 2014/2015 epidemic season in poland. the study was part of the virological surveillance systems - sentinel and non-sentinel. a positive result for virological infection was obtained in 50.9 % of samples tested. the distribution of ...201626987329
molecular characterization of a novel reassortant h1n2 influenza virus containing genes from the 2009 pandemic human h1n1 virus in swine from eastern china.pandemic outbreaks of h1n1 swine influenza virus have been reported since 2009. reassortant h1n2 viruses that contain genes from the pandemic h1n1 virus have been isolated in italy and the united states. however, there is limited information regarding the molecular characteristics of reassortant h1n2 swine influenza viruses in eastern china. active influenza surveillance programs in zhejiang province identified a novel h1n2 influenza virus isolated from pigs displaying clinical signs of influenz ...201626980674
detailed report on 2014/15 influenza virus characteristics, and estimates on influenza virus vaccine effectiveness from austria's sentinel physician surveillance network.influenza vaccine effectiveness (ve) is influenced by the antigenic similarity between vaccine- and circulating strains.201626975056
antigenic drift of a/h3n2/virus and circulation of influenza-like viruses during the 2014/2015 influenza season in poland.morbidity rates of influenza could be greatly reduced due to vaccination. however, the virus is able to evolve through genetic mutations, which is why vaccines with updated composition are necessary every season. their effectiveness depends on whether there is a good antigenic match between circulating viruses and vaccine strains. in poland, the 2014/2015 influenza epidemic started in week 5 (january/february) of 2015 and continued until week 17 (april) of 2015. the influenza activity was modera ...201626956457
a novel small-molecule inhibitor of influenza a virus acts by suppressing pa endonuclease activity of the viral polymerase.the rna-dependent rna polymerase of influenza a virus comprises conserved and independently-folded subdomains with defined functionalities. the n-terminal domain of the pa subunit (pa(n)) harbors the endonuclease function so that it can serve as a desired target for drug discovery. to identify a class of anti-influenza inhibitors that impedes pa(n) endonuclease activity, a screening approach that integrated the fluorescence resonance energy transfer based endonuclease inhibitory assay with the d ...201626956222
induction of systemic and mucosal immunity and maintenance of its memory against influenza a virus by nasal vaccination using a new mucosal adjuvant sf-10 derived from pulmonary surfactant in young cynomolgus monkeys.induction of systemic and mucosal immunity and maintenance of its memory was investigated in 12 young male cynomolgus monkeys after intranasal instillation of flu vaccine using a new mucosal adjuvant sf-10 derived from pulmonary surfactant constituents. split-product of influenza virus a/california/7/2009(h1n1)pdm hemagglutinin vaccine (hav) at 15 μg with or without sf-10 and the adjuvant alone were instilled intranasally three times every 2 weeks. sf-10-adjuvanted hav (sf-10-hav) elicited signi ...201626954466
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
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
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
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
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
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
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
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
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
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
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
[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
[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
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
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
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
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
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
identification of combinatorial host-specific signatures with a potential to affect host adaptation in influenza a h1n1 and h3n2 subtypes.the underlying strategies used by influenza a viruses (iavs) to adapt to new hosts while crossing the species barrier are complex and yet to be understood completely. several studies have been published identifying singular genomic signatures that indicate such a host switch. the complexity of the problem suggested that in addition to the singular signatures, there might be a combinatorial use of such genomic features, in nature, defining adaptation to hosts.201627473048
effect of statin use on influenza vaccine effectiveness.recent studies suggest that statin use may reduce influenza vaccine effectiveness (ve), but laboratory-confirmed influenza was not assessed.201627471318
neutralization and binding profile of monoclonal antibodies generated against influenza a h1n1 viruses.monoclonal antibodies (mabs) provide scope for the development of better therapeutics and diagnostic tools. herein, we describe the binding and neutralization profile(s) for a panel of murine mabs generated against influenza a h1n1 viruses elicited by immunization with pandemic h1 recombinant hemagglutinin (rha)/whole virus or seasonal h1 rha. neutralizing mabs, ma-2070 and ma-m, were obtained after pandemic a/california/07/2009 (h1n1) virus/rha immunization(s). both mabs reacted specifically wi ...201627463230
highly sensitive detection of influenza virus by boron-doped diamond electrode terminated with sialic acid-mimic peptide.the progression of influenza varies according to age and the presence of an underlying disease; appropriate treatment is therefore required to prevent severe disease. anti-influenza therapy, such as with neuraminidase inhibitors, is effective, but diagnosis at an early phase of infection before viral propagation is critical. here, we show that several dozen plaque-forming units (pfu) of influenza virus (ifv) can be detected using a boron-doped diamond (bdd) electrode terminated with a sialic aci ...201627457924
fluzone® intradermal quadrivalent influenza vaccine.an intradermal version of fluzone® split-virion inactivated trivalent influenza vaccine, containing 9 µg hemagglutinin per strain of a/h1n1, a/h3n2, and one b lineage virus (fluzone intradermal, sanofi pasteur), became available in the us during the 2011-2012 influenza season for adults 18-64 years of age. in advance of the 2015-2016 season, fluzone intradermal was replaced with fluzone intradermal quadrivalent vaccine, which contains 9 µg hemagglutinin per strain of the two a-strain viruses and ...201627457797
age-specific genetic and antigenic variations of influenza a viruses in hong kong, 2013-2014.age-specific genetic and antigenic variations of influenza viruses have not been documented in tropical and subtropical regions. we implemented a systematic surveillance program in two tertiary hospitals in hong kong island, to collect 112 a(h1n1)pdm09 and 254 a(h3n2) positive specimens from 2013 to 2014. of these, 56 and 72 were identified as genetic variants of the who recommended vaccine composition strains, respectively. a subset of these genetic variants was selected for hemagglutination-in ...201627453320
the pb2 subunit of the influenza a virus rna polymerase is imported into the mitochondrial matrix.the polymerase basic 2 (pb2) subunit of the rna polymerase complex of seasonal human influenza a viruses has been shown to localize to the mitochondria. various roles, including the regulation of apoptosis and innate immune responses to viral infection, have been proposed for mitochondrial pb2. in particular, pb2 has been shown to inhibit interferon expression by associating with the mitochondrial antiviral signaling (mavs) protein, which acts downstream of rig-i and mda-5 in the interferon indu ...201627440905
evaluating the case for trivalent or quadrivalent influenza vaccines.influenza viruses circulate widely throughout the world and it is estimated that they affect between 5 and 15% of the population annually. since 1977, four viruses co-circulate - two a viruses (h1n1 and h3n2) and two b viruses (b yamagata and b victoria). type a viruses generally cause up to two thirds of annual infections, although single country studies have shown that b infections may be the predominant virus in the one year in four. influenza vaccines have traditionally included the hamagglu ...201627435025
anti-hemagglutinin antibody derived lead peptides for inhibitors of influenza virus binding.antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. however, development, production and quality control of antibodies is expensive and time consuming. to circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza a spike glycoprotein. their binding properties were studied experimentally, and by molecular dynamics simulations. two peptide ...201627415624
influenza virus a(h1n1)2009 antibody-dependent cellular cytotoxicity in young children prior to the h1n1 pandemic.pre-existing immunity played a significant role in protection during the latest influenza a virus h1n1 pandemic, especially in older age groups. structural similarities were found between a(h1n1)2009 and older h1n1 virus strains to which humans had already been exposed. broadly cross-reactive antibodies capable of neutralizing the a(h1n1)2009 virus have been implicated in this immune protection in adults. we investigated the serological profile of a group of young children aged 9 years (n=55), f ...201627412007
probing the impact of quercetin-7-o-glucoside on influenza virus replication influence.influenza virus is still at large and seriously affects social welfare and health. dianthus superbus is a well-known medicinal plant widely used in mongolian and chinese traditional medicine for anti-inflammatory purposes.201627387404
a novel endonuclease inhibitor exhibits broad-spectrum anti-influenza virus activity in vitro.antiviral drugs are important in preventing and controlling influenza, particularly when vaccines are ineffective or unavailable. a single class of antiviral drugs, the neuraminidase inhibitors (nais), is recommended for treating influenza. the limited therapeutic options and the potential risk of antiviral resistance are driving the search for additional small-molecule inhibitors that act on influenza virus proteins. the acid polymerase (pa) of influenza viruses is a promising target for new an ...201627381402
integrated microfluidic device using a single universal aptamer to detect multiple types of influenza viruses.dna aptamers that can bind specific molecular targets have great potential as probes for microbial diagnostic applications. however, aptamers may change their conformation under different operating conditions, thus affecting their affinity and specificity towards the target molecules. in this study, a new integrated microfluidic system was developed that exploited the predictable change in conformation of a single universal influenza aptamer exposed to differing ion concentrations in order to de ...201627376195
the emergence and consistency of influenza strains causing influenza like illness in himachal pradesh, india.the present study offers the status of ongoing surveillance influenza at national influenza surveillance centre (nisc), central research institute (cri), kasauli for the emergence and consistency of influenza strains for current as well as over a period of three decades in solan, himachal pradesh. from 1980 to 2015, various clinical centers of himachal reported counts of influenza-like illness (fever including cough or sore throat). during these years, the respiratory specimens of 6581 patients ...201627366763
determination of current reference viruses for serological study of swine influenza viruses after the introduction of pandemic 2009 h1n1 (pdmh1n1) in thailand.since the introduction of pandemic h1n1 2009 virus (pdmh1n1) in pigs, the status of thai swine influenza virus (siv) has changed. the pdmh1n1 and its reassortant viruses have become the predominant strain circulating in the thai swine population based on the surveillance data from 2012 to 2014. for this reason, the reference viruses for serological assays using the hemagglutination inhibition (hi) test needed to be updated. six anti-sera against reference viruses from 2006 to 2009 (enh1n1-06, en ...201627355862
generation and protective ability of influenza virus-specific antibody-dependent cellular cytotoxicity in humans elicited by vaccination, natural infection, and experimental challenge.nonneutralizing antibodies (abs) involved in antibody-dependent cellular cytotoxicity (adcc) may provide some protection from influenza virus infection. the ability of influenza vaccines to induce adcc-mediating abs (adcc-abs) in adults and children is unclear.201627354365
is the onset of influenza in the community age-related?we studied the spread of influenza in the community between 1993 and 2009 using primary-care surveillance data to investigate if the onset of influenza was age-related. virus detections [a(h3n2), b, a(h1n1)] and clinical incidence of influenza-like illness (ili) in 12·3 million person-years in the long-running royal college of general practitioners-linked clinical-virological surveillance programme in england & wales were examined. the number of days between symptom onset and the all-age peak il ...201627350234
safety and immunogenicity of 3 seasonal trivalent influenza vaccines in the chinese military.influenza, caused by the influenza virus, is a contagious acute viral respiratory disease with a high incidence rate and wide and rapid spread. influenza-related morbidity, mortality, and hospitalization rates remain high and are increasing continuously in high-risk groups, with a significant impact on human health and the economy. in order to evaluate the immunogenicity of 3 seasonal trivalent influenza vaccines in chinese military, we conducted this field trial. we assessed the safety and immu ...201627348250
influenza a viruses detected in swine in southern germany after the h1n1 pandemic in 2009.infections with influenza a viruses (iav) are highly prevalent in swine populations, and stable cocirculation of at least three lineages has been well documented in european swine - till 2009. however, since the emergence of the human pandemic pdmh1n1 virus in 2009, which has been (re)introduced into individual swine herds worldwide, the situation has been changing. these variations in the respective iav pools within pig populations are of major interest, and the zoonotic potential of putative e ...201627334519
eyedrop vaccination induced systemic and mucosal immunity against influenza virus in ferrets.we investigated eyedrop vaccination (edv) in pre-clinical development for immunological protection against influenza and for potential side effects involving ocular inflammation and the central nervous system (cns). live attenuated influenza edv, ca07 (h1n1), pz-4 (h1n2) and uruguay (h3n2), induced both systemic and mucosal virus-specific antibody responses in ferrets. in addition, edv resulted in a clinically significant protection against viral challenge, and suppression of viral replication i ...201627333331
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