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viral etiology of influenza-like illnesses during the influenza season between december 2011 and april 2012.the aim of this study was to determine the frequency of respiratory viruses responsible for respiratory tract infections in turkish children during the 2011-2012 influenza season. nasal swabs were obtained from patients with symptoms suggestive of an influenza-like illness between december 2011 and april 2012. samples were analyzed with multiplex real-time polymerase chain reaction (rt-pcr) to help identify the causative viral pathogen. a total of 200 patients were enrolled in the study. a respi ...201424105787
standard trivalent influenza virus protein vaccination does not prime antibody-dependent cellular cytotoxicity in macaques.yearly vaccination with the trivalent inactivated influenza vaccine (tiv) is recommended, since current vaccines induce little cross neutralization to divergent influenza strains. whether the tiv can induce antibody-dependent cellular cytotoxicity (adcc) responses that can cross-recognize divergent influenza virus strains is unknown. we immunized 6 influenza-naive pigtail macaques twice with the 2011-2012 season tiv and then challenged the macaques, along with 12 control macaques, serially with ...201324109221
signal-processing-based bioinformatics approach for the identification of influenza a virus subtypes in neuraminidase genes.neuraminidase (na) genes of influenza a virus is a highly potential candidate for antiviral drug development that can only be realized through true identification of its sub-types. in this paper, in order to accurately detect the sub-types, a hybrid predictive model is therefore developed and tested over proteins obtained from the four subtypes of the influenza a virus, namely, h1n1, h2n2, h3n2 and h5n1 that caused major pandemics in the twentieth century. the predictive model is built by the fo ...201324110375
subcellular proteomic analysis of human host cells infected with h3n2 swine influenza virus.cross-species transmissions of swine influenza viruses (sivs) raise great public health concerns. in this study, subcellular proteomic profiles of human a549 cells inoculated with h3n2 subtype siv were used to characterize dynamic cellular responses to infection. by 2de and ms, 27 differentially expressed (13 upregulated, 14 downregulated) cytoplasmic proteins and 20 differentially expressed (13 upregulated, 7 downregulated) nuclear proteins were identified. gene ontology analysis suggested that ...201324115376
epidemiology of seasonal influenza in bangkok between 2009 and 2012.this study investigated influenza activity in bangkok, thailand between june 2009 and july 2012.201324129626
efficacy of a levulinic acid plus sodium dodecyl sulfate (sds)-based sanitizer on inactivation of influenza a virus on eggshells.influenza a virus poses a major public health concern and is associated with annual epidemics and occasional pandemics. influenza a h3n2 viruses, which are an important cause of human influenza, can infect birds and mammals. contaminated undercooked poultry products including eggs with avian influenza virus constitute a possible risk of transmission to humans. in this study, a novel levulinic acid plus sodium dodecyl sulfate (sds) sanitizer was evaluated for eggshell decontamination. influenza a ...201324132876
treatment of influenza virus with beta-propiolactone alters viral membrane fusion.beta-propiolactone (bpl) is commonly used as an inactivating reagent to produce viral vaccines. although bpl has been described to chemically modify nucleic acids, its effect on viral proteins, potentially affecting viral infectivity, remains poorly studied. here, a h3n2 strain of influenza virus was submitted to treatment with various bpl concentrations (2-1000μm). cell infectivity was progressively reduced and entirely abolished at 1mm bpl. virus fusion with endosome being a critical step in v ...201424140008
longitudinal analysis of leukocyte differentials in peripheral blood of patients with acute respiratory viral infections.leukocyte counts and differentials are commonly acquired in patients with suspected respiratory viral infections and may contribute diagnostic information. however, most published work is limited to a single timepoint at initial presentation to a medical provider, which may correspond to widely varying points in the course of disease.201324140015
the kinase mtor modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus.highly pathogenic avian influenza viruses pose a continuing global threat. current vaccines will not protect against newly evolved pandemic viruses. the creation of 'universal' vaccines has been unsuccessful because the immunological mechanisms that promote heterosubtypic immunity are incompletely defined. we found here that rapamycin, an immunosuppressive drug that inhibits the kinase mtor, promoted cross-strain protection against lethal infection with influenza virus of various subtypes when a ...201324141387
administration of as03b-adjuvanted a(h1n1)pdm09 vaccine in children aged <3 years enhances antibody response to h3 and b viruses following a single dose of trivalent vaccine one year later.we report on a follow-up clinical and serological investigation of 274 children who received seasonal influenza vaccine (trivalent inactivated vaccine [tiv]) 1 year after receipt of either as03(b)-adjuvanted subunit or whole virus monovalent a(h1n1)pdm09 vaccine and describe the antibody responses to the h3n2 a/perth/16/2009 and b/brisbane/60/2008 components of tiv.201424149079
molecular epidemiology of influenza a virus infection in cyprus in four consecutive seasons (2009 pandemic-2013).the aim of this study was to investigate the epidemiology of influenza a virus infection in cyprus from the 2009 pandemic until 2013. pandemic influenza a(h1n1)2009 virus infections outnumbered infections with other respiratory viruses until the end of 2009. the pandemic virus was also the prevalent influenza strain during influenza season 2010-2011; however, it was completely replaced by h3n2 subtype in the next season. during the most recent influenza season, 2012-2013, the pandemic strain was ...201424152574
newly emerging mutations in the matrix genes of the human influenza a(h1n1)pdm09 and a(h3n2) viruses reduce the detection sensitivity of real-time reverse transcription-pcr.new variants of the influenza a(h1n1)pdm09 and a(h3n2) viruses were detected in taiwan between 2012 and 2013. some of these variants were not detected in clinical specimens using a common real-time reverse transcription-pcr (rt-pcr) assay that targeted the conserved regions of the viral matrix (m) genes. an analysis of the m gene sequences of the new variants revealed that several newly emerging mutations were located in the regions where the primers or probes of the real-time rt-pcr assay bind; ...201424153120
activation of influenza a viruses by host proteases from swine airway epithelium.pigs are important natural hosts of influenza a viruses, and due to their susceptibility to swine, avian, and human viruses, they may serve as intermediate hosts supporting adaptation and genetic reassortment. cleavage of the influenza virus surface glycoprotein hemagglutinin (ha) by host cell proteases is essential for viral infectivity. most influenza viruses, including human and swine viruses, are activated at a monobasic ha cleavage site, and we previously identified tmprss2 and hat to be re ...201424155384
plc-γ1 signaling plays a subtype-specific role in postbinding cell entry of influenza a virus.host signaling pathways and cellular proteins play important roles in the influenza viral life cycle and can serve as antiviral targets. in this study, we report the engagement of host phosphoinositide-specific phospholipase γ1 (plc-γ1) in mediating cell entry of influenza virus h1n1 but not h3n2 subtype. both plc-γ1-specific inhibitor and short hairpin rna (shrna) strongly suppress the replication of h1n1 but not h3n2 viruses in cell culture, suggesting that plc-γ1 plays an important subtype-sp ...201424155396
receptor binding and ph stability - how influenza a virus hemagglutinin affects host-specific virus infection.influenza a virus strains adopt different host specificities mainly depending on their hemagglutinin (ha) protein. via ha, the virus binds sialic acid receptors of the host cell and, upon endocytic uptake, ha triggers fusion between the viral envelope bilayer and the endosomal membrane by a low ph-induced conformational change leading to the release of the viral genome into the host cell cytoplasm. both functions are crucial for viral infection enabling the genesis of new progeny virus. adaptati ...201424161712
the anti-influenza virus effect of phellinus igniarius extract.herbal medicine has been used in the orient for thousands of years to treat large and small ailments, including microbial infections. although there are treatments for influenza virus infection, there is no treatment for drug-resistant viruses. it is time that we explored and exploited the multi-component nature of herbal extracts as multi-drug combination therapies. here, we present data on the anti-influenza virus effect of a medicinal mushroom, phellinus igniarius. the p. igniarius water extr ...201324173646
loss and gain of n-linked glycosylation sites in globular head and stem of ha found in a/h3n2 flu fatal and severe cases during 2013 tunisia flu seasonal survey.glycosylation on the globular head of the hemagglutinin (ha) protein of influenza virus acts as an important target for recognition and destruction of virus by innate immune proteins of the collectin family. in the current study, we have characterized the dynamic amino acid changes at n-linked glycosylation sites of full length sequences of ha genes of 5 a/h3n2 tunisian strains isolates from mild, severe, and fatal cases. compared to the reference strain, a/perth/16/2009 substitutions in potenti ...201424174280
serum antibody response to influenza virus vaccination during chemotherapy treatment in adult patients with solid tumours.higher rates of hospitalization and mortality are described in oncology patients with influenza virus infection compared to the general population. yearly influenza vaccination is recommended for patients treated with chemotherapy. the optimal moment to administer the vaccine during a treatment cycle has not been studied extensively.201324176495
phase i/ii trial of a replication-deficient trivalent influenza virus vaccine lacking ns1.the non-structural protein ns1 of the influenza virus counteracts the interferon-mediated immune response of the host. we investigated the safety and immunogenicity of a trivalent formulation containing influenza h1n1, h3n2 and b strains lacking ns1 (delns1-trivalent).201324183981
kinetics of influenza a virus nucleoprotein antibody (igm, iga, and igg) in serum and oral fluid specimens from pigs infected under experimental conditions.indirect influenza a virus (iav) nucleoprotein (np) antibody elisas were used to compare the kinetics of the np igm, iga, and igg responses in serum and pen-based oral fluid samples collected from 82 pigs followed for 42 days post inoculation (dpi). treatment categories included vaccination (0, 1) and inoculation (0, 1) with contemporary h1n1 or h3n2 isolates. antibody ontogeny was markedly affected by vaccination status, but no significant differences were detected between h1n1 and h3n2 inocula ...201324200976
inhibition of a/human/hubei/3/2005 (h3n2) influenza virus infection by silver nanoparticles in vitro and in vivo.silver nanoparticles (agnps) have attracted much attention as antimicrobial agents and have demonstrated efficient inhibitory activity against various viruses, including human immunodeficiency virus, hepatitis b virus, and tacaribe virus. in this study, we investigated if agnps could have antiviral and preventive effects in a/human/hubei/3/2005 (h3n2) influenza virus infection. madin-darby canine kidney cells infected with agnp-treated h3n2 influenza virus showed better viability (p<0.05 versus ...201324204140
epidemiological surveillance of low pathogenic avian influenza virus (lpaiv) from poultry in guangxi province, southern china.low pathogenic avian influenza virus (lpaiv) usually causes mild disease or asymptomatic infection in poultry. however, some lpaiv strains can be transmitted to humans and cause severe infection. genetic rearrangement and recombination of even low pathogenic influenza may generate a novel virus with increased virulence, posing a substantial risk to public health. southern china is regarded as the world "influenza epicenter", due to a rash of outbreaks of influenza in recent years. in this study, ...201324204754
comparison of mutation patterns in full-genome a/h3n2 influenza sequences obtained directly from clinical samples and the same samples after a single mdck passage.human influenza viruses can be isolated efficiently from clinical samples using madin-darby canine kidney (mdck) cells. however, this process is known to induce mutations in the virus as it adapts to this non-human cell-line. we performed a systematic study to record the pattern of mdck-induced mutations observed across the whole influenza a/h3n2 genome. seventy-seven clinical samples collected from 2009-2011 were included in the study. two full influenza genomes were obtained for each sample: o ...201324223916
detection and isolation of airborne influenza a h3n2 virus using a sioutas personal cascade impactor sampler.the air we breathe contains microorganisms that can cause infectious respiratory diseases. after two occupants of an apartment were diagnosed with influenza in february of 2013, efforts were made to detect and isolate airborne influenza virus using two different types of active air samplers: a sioutas personal cascade impactor sampler (pcis) and an skc biosampler. the pcis collects size-fractionated particles by impaction on polytetrafluoroethylene filters, whereas the skc biosampler collects ai ...201324224087
comparison of influenza a virus infection in high- and low-birth-weight pigs using morphometric analysis.epigenetic studies have shown that low-birth-weight (lbw) and growth restriction has been associated with reduced immune function in humans and reduced passive immunity in pigs. to examine the immune responses of high-birth-weight (hbw) and lbw groups of pigs, influenza a virus infection was used as an exemplifier of neonatal respiratory disease.201324224813
swine influenza: clinical, serological, pathological, and virological cross-sectional studies in nine farms in argentina.influenza a viruses (iav) are important pathogens responsible for economic losses in the swine industry and represent a threat to public health. in argentina, clinical, pathological, and virological findings suggest that iav infection is widespread among pig farms. in addition, several subtypes of iav, such as ph1n1, h3n2, δ1h1n1, and δ2h1n2, have been reported.201324224814
swine influenza virus vaccine serologic cross-reactivity to contemporary us swine h3n2 and efficacy in pigs infected with an h3n2 similar to 2011-2012 h3n2v.swine influenza a virus (iav) reassortment with 2009 h1n1 pandemic (h1n1pdm09) virus has been documented, and new genotypes and subclusters of h3n2 have since expanded in the us swine population. an h3n2 variant (h3n2v) virus with the h1n1pdm09 matrix gene and the remaining genes of swine triple reassortant h3n2 caused outbreaks at agricultural fairs in 2011-2012.201324224818
population dynamics of cocirculating swine influenza a viruses in the united states from 2009 to 2012.understanding the ecology and evolution of influenza a viruses (iav) in mammalian hosts is critical to reduce disease burden in production animals and lower zoonotic infection risk in humans. recent advances in influenza surveillance in us swine populations allow for timely epidemiological, phylogenetic, and virological analyses that monitor emergence of novel viruses and assess changes in viral population dynamics.201324224819
replication characteristics of swine influenza viruses in precision-cut lung slices reflect the virulence properties of the viruses.precision-cut lung slices of pigs were infected with five swine influenza a viruses of different subtypes (a/sw/potsdam/15/1981 h1n1, a/sw/bad griesbach/idt5604/2006 h1n1, a/sw/bakum/1832/2000 h1n2, a/sw/damme/idt5673/2006 h3n2, a/sw/herford/idt5932/2007 h3n2). the viruses were able to infect ciliated and mucus-producing cells. the infection of well-differentiated respiratory epithelial cells by swine influenza a viruses was analyzed with respect to the kinetics of virus release into the superna ...201324225030
assessment for possible healthcare-associated transmission of a new variant influenza virus--pennsylvania, august 2011.in august 2011, one of the earliest cases of influenza a(h3n2) variant [a(h3n2)v] virus infection was hospitalized with severe illness. to investigate the potential for healthcare-associated transmission of influenza a(h3n2)v, we evaluated both healthcare providers and patient contacts of the case. we found that healthcare-associated transmission was unlikely.201324225616
incorporation of a proteotyping approach using mass spectrometry for surveillance of influenza virus in cell-cultured strains.the reemergence of deadly pandemic influenza virus strains has necessitated the development of improved methods for rapid detection and subtyping of influenza viruses that will enable more strains to be characterized at the molecular level. representative circulating strains of human influenza viruses from primary clinical specimens were grown in cell culture, purified through polyethylene glycol precipitation, proteolytically digested with an endoproteinase, and analyzed and identified by high- ...201424226917
novel h7n9 influenza virus shows low infectious dose, high growth rate, and efficient contact transmission in the guinea pig model.the zoonotic outbreak of h7n9 subtype avian influenza virus that occurred in eastern china in the spring of 2013 resulted in 135 confirmed human cases, 44 of which were lethal. sequencing of the viral genome revealed a number of molecular signatures associated with virulence or transmission in mammals. we report here that, in the guinea pig model, a human isolate of novel h7n9 influenza virus, a/anhui/1/2013 (an/13), is highly dissimilar to an h7n1 avian isolate and instead behaves similarly to ...201424227867
genome sequence of a circulating human-like swine-origin influenza a virus h3n2 strain.the full-genome sequence of a/swine/henan/1/2010, a strain of influenza a virus isolated in central china, was determined. phylogenetic analyses show that its eight genomic segments are human-like, and some of its segments have appeared in swine h1n2, swine h1n1, and human h1n2 influenza viruses.201324233586
influenza vaccine effectiveness in the 2011-2012 season: protection against each circulating virus and the effect of prior vaccination on estimates.each year, the us influenza vaccine effectiveness network examines the effectiveness of influenza vaccines in preventing medically attended acute respiratory illnesses caused by influenza.201424235265
immunization of rabbits with synthetic peptides derived from a highly conserved β-sheet epitope region underneath the receptor binding site of influenza a virus.there is increasing concern about the speed with which health care providers can administer prophylaxis and treatment in an influenza pandemic. generally, it takes several months to manufacture an influenza vaccine by propagation of the virus in chicken eggs or cultured cells. newer, faster protocols for the production of vaccines that induce broad-spectrum immunity are therefore highly desirable. we previously developed human monoclonal antibody b-1 that shows broadly neutralizing activity agai ...201324235814
humoral and cellular responses to a non-adjuvanted monovalent h1n1 pandemic influenza vaccine in hospital employees.the efficacy of the h1n1 influenza vaccine relies on the induction of both humoral and cellular responses. this study evaluated the humoral and cellular responses to a monovalent non-adjuvanted pandemic influenza a/h1n1 vaccine in occupationally exposed subjects who were previously vaccinated with a seasonal vaccine.201324238117
genomic analysis of influenza a virus from captive wild boars in brazil reveals a human-like h1n2 influenza virus.influenza is a viral disease that affects human and several animal species. in brazil, h1n1, h3n2 and 2009 pandemic h1n1 a(h1n1)pdm09 influenza a viruses (iav) circulate in domestic swine herds. wild boars are also susceptible to iav infection but in brazil until this moment there are no reports of iav infection in wild boars or in captive wild boars populations. herein the occurrence of iav in captive wild boars with the presence of lung consolidation lesions during slaughter was investigated. ...201424238665
a serological survey of canine h3n2, pandemic h1n1/09 and human seasonal h3n2 influenza viruses in dogs in china.influenza viruses have been isolated from dogs in china; however, the extent of influenza infection among dogs is not yet clear. here, we examined the seroprevalence of avian-origin canine h3n2, pandemic h1n1/09 and human seasonal h3n2 influenza viruses in pet dogs in china during january 2012 to june 2013. the seropositivity rate of canine h3n2, h1n1/09 and human h3n2 were 3.5%, 1.5%, and 1.2%, respectively. dogs aged 2-5 years were most commonly seropositive to canine h3n2 virus. it is worth n ...201424239170
the effect of the mdck cell selected neuraminidase d151g mutation on the drug susceptibility assessment of influenza a(h3n2) viruses.propagation of influenza a(h3n2) viruses in mdck cells has been associated with the emergence of neuraminidase (na) variants carrying a change at residue 151. in this study, the pyrosequencing assay revealed that ∼90% of a(h3n2) virus isolates analyzed (n=150) contained more than one amino acid variant (d/g/n) at position 151. susceptibilities of the virus isolates to zanamivir and oseltamivir were assessed using the chemiluminescent and fluorescent na inhibition (ni) assays. in the chemilumines ...201424239666
immunogenicity and safety of an inactivated 2012/2013 trivalent influenza vaccine produced in mammalian cell culture (optaflu®): an open label, uncontrolled study.the present study aimed to evaluate immunogenicity and safety of the 2012/2013 seasonal influenza vaccine (optaflu(®)) after the world health organization recommended two new strains for the composition.201424240428
human cytotoxic t lymphocytes directed to seasonal influenza a viruses cross-react with the newly emerging h7n9 virus.in february 2013, zoonotic transmission of a novel influenza a virus of the h7n9 subtype was reported in china. although at present no sustained human-to-human transmission has been reported, a pandemic outbreak of this h7n9 virus is feared. since neutralizing antibodies to the hemagglutinin (ha) globular head domain of the virus are virtually absent in the human population, there is interest in identifying other correlates of protection, such as cross-reactive cd8(+) t cells (cytotoxic t lympho ...201424257602
influenza virus surveillance in pakistan during 2008-2011.there is little information about influenza among the pakistani population. in order to assess the trends of influenza-like-illness (ili) and to monitor the predominant circulating strains of influenza viruses, a country-wide lab-based surveillance system for ili and severe acute respiratory illness (sari) with weekly sampling and reporting was established in 2008. this system was necessary for early detection of emerging novel influenza subtypes and timely response for influenza prevention and ...201324260327
substitutions near the receptor binding site determine major antigenic change during influenza virus evolution.the molecular basis of antigenic drift was determined for the hemagglutinin (ha) of human influenza a/h3n2 virus. from 1968 to 2003, antigenic change was caused mainly by single amino acid substitutions, which occurred at only seven positions in ha immediately adjacent to the receptor binding site. most of these substitutions were involved in antigenic change more than once. equivalent positions were responsible for the recent antigenic changes of influenza b and a/h1n1 viruses. substitution of ...201324264991
avian influenza virus h3 hemagglutinin may enable high fitness of novel human virus reassortants.reassortment of influenza a virus genes enables antigenic shift resulting in the emergence of pandemic viruses with novel hemagglutinins (ha) acquired from avian strains. here, we investigated whether historic and contemporary avian strains with different replication capacity in human cells can donate their hemagglutinin to a pandemic human virus. we performed double-infections with two avian h3 strains as ha donors and a human acceptor strain, and determined gene compositions and replication of ...201324265752
selection of dna aptamers that bind to influenza a viruses with high affinity and broad subtype specificity.many cases of influenza are reported worldwide every year. the influenza virus often acquires new antigenicity, which is known as antigenic shift; this results in the emergence of new virus strains, for which preexisting immunity is not found in the population resulting in influenza pandemics. in the event a new strain emerges, diagnostic tools must be developed rapidly to detect the novel influenza strain. the generation of high affinity antibodies is costly and takes time; therefore, an altern ...201424269231
protease-dependent hemagglutinin cleavage contributes to alteration in chicken hemagglutination by the h3n2 influenza a virus.the human influenza a virus (h3n2) has been the predominant influenza strain since 1992, and one property of this virus is non-agglutination of chicken erythrocytes [ch(-) virus]. the ch(-) virus in our study was able to acquire chicken hemagglutination [ch(+)] by trypsin passage but not by chymotrypsin passage. moreover, the trypsin-passaged ch(+) viruses reacquired the ch(-) property after a further chymotrypsin passage. in particular, genetic analysis showed no evidence of mutations in the he ...201324270143
seroprevalence of a novel influenza a (h3n2) variant virus in the japanese population.antibody distribution to a novel swine-origin influenza a (h3n2) variant virus among different age groups in japan was determined by hemagglutination-inhibition assay. japanese children in the age group 1-14 years were at a higher risk than those in older age groups.201324270150
anti-influenza activity of alchemilla mollis extract: possible virucidal activity against influenza virus particles.influenza virus infection is a major public health problem that leads to significant morbidity and mortality. the emergence of resistance to the currently available anti-influenza agents has necessitated the development of new drugs with novel targets. studying known ethno-medicinal plants is a promising approach for the discovery of new antiviral compounds. alchemilla mollis is used in traditional medicine in europe for different indications, including minimizing the symptoms of a sore throat. ...201324270383
recombinant influenza a h3n2 viruses with mutations of ha transmembrane cysteines exhibited altered virological characteristics.influenza a h3n2 virus as the cause of 1968 pandemic has since been circulating in human and swine. our earlier study has shown that mutations of one or two cysteines in the transmembrane domain of h3 hemagglutinin (ha) affected the thermal stability and fusion activity of recombinant ha proteins. here, we report the successful generation of three recombinant h3n2 mutant viruses (c540s, c544l, and 2c/sl) with mutations of one or two transmembrane cysteines of ha in the background of a/swine/guan ...201424272698
synthesis of 1,2,3-triazolyl nucleoside analogs as potential anti-influenza a (h3n2 subtype) virus agents.montmorillonite k10 impregnated with copper dichloride and potassium iodide (cucl2 /ki/k10) was used as catalyst in the cycloaddition of azides and propargylnucleobases, to provide the corresponding 1,4-disubstituted 1,2,3-triazoles in good yield. all compounds 16-23 were evaluated for their antiviral activity in vitro. compound 18 showed moderate inhibition against influenza virus a (h3n2).201424272912
development and evaluation of a sybr green-based real time rt-pcr assay for detection of the emerging avian influenza a (h7n9) virus.most recently a novel avian-origin influenza a (h7n9) virus emerged in china and has been associated with lots of human infection and fatal cases. genetic analysis of the viral genome revealed that this reassortant virus might be better adapted to humans than other avian influenza viruses. molecular diagnostic methods are thus urgently needed in public health laboratories. in this study, a sybr green-based one-step real time reverse transcription-pcr (rt-pcr) was developed to detect the novel h7 ...201324278234
genetic mutations in influenza h3n2 viruses from a 2012 epidemic in southern china.an influenza h3n2 epidemic occurred throughout southern china in 2012.201324279698
homosecoiridoid alkaloids with amino acid units from the flower buds of lonicera japonica.nine new homosecoiridoid alkaloids, named lonijaposides o-w (1-9), along with 19 known compounds, were isolated from an aqueous extract of the flower buds of lonicera japonica. their structures and absolute configurations were determined by spectroscopic data analysis and chemical methods. lonijaposides o-w have structural features that involve amino acid units sharing the n atom with a pyridinium (1-5) or nicotinic acid (6-9) moiety. the absolute configurations of the amino acid units were dete ...201324279769
influenza vaccine response in adults exposed to perfluorooctanoate and perfluorooctanesulfonate.supported by several epidemiological studies and a large number of animal studies, certain polyfluorinated alkyl acids are believed to be immunotoxic, affecting particularly humoral immunity. our aim was to investigate the relationship between the antibody response following vaccination with an inactivated trivalent influenza vaccine and circulating levels of perfluorooctanoate (pfoa) and perfluorooctanesulfonate (pfos). the study population consisted of 411 adults living in the mid-ohio region ...201424284791
different evolutionary trends of swine h1n2 influenza viruses in italy compared to european viruses.european h1n2 swine influenza viruses (eu h1n2sivs) arose from multiple reassortment events among human h1n1, human h3n2, and avian influenza viruses. we investigated the evolutionary dynamics of 53 italian h1n2 strains by comparing them with eu h1n2 sivs. hemagglutinin (ha) phylogeny revealed italian strains fell into four groups: group a and b (41 strains) had a human h1 similar to eu h1n2sivs, which probably originated in 1986. however group b (38 strains) formed a subgroup that had a two-ami ...201324289094
the use of antiviral drugs for influenza: guidance for practitioners 2012/2013.the present article addresses the use of antiviral drugs in the management of seasonal influenza illness for the 2012/2013 season. it updates the previous document published in 2011 (1). noteworthy guidance updates since 2011 include the following: seasonal influenza in 2012/2013 is predicted to be caused by two human influenza a and one influenza b strain, all of which are anticipated to remain generally susceptible to oseltamivir.the predicted strains are a/california/7/2009 (h1n1) pdm09-like, ...201224294283
avian-origin h3n2 canine influenza virus circulating in farmed dogs in guangdong, china.since 2006, more and more cases of the infectious h3n2 canine influenza virus (civ) in pet dogs have been reported in southern china. however, little is known about the prevalence situation of h3n2 civ infections in farmed dogs in china. this is the first systematic epidemiological surveillance of civ in different dog populations in southern china. two virus strains a/canine/guangdong/1/2011(h3n2) and a/canine/guangdong/5/2011(h3n2) were isolated from canine nasal swabs collected at one dog farm ...201324298574
drug susceptibility surveillance of influenza viruses circulating in the united states in 2011-2012: application of the who antiviral working group criteria.assessing susceptibility of influenza viruses to neuraminidase (na) inhibitors (nais) is primarily done in na inhibition (ni) assays, supplemented by na sequence analysis. however, two factors present challenges for ni assay data interpretation: lack of established ic50 values indicative of clinically relevant resistance and insufficient harmonization of ni testing methodologies among surveillance laboratories. in 2012, the who working group on influenza antiviral susceptibility (who-avwg) devel ...201424299049
comparative analysis of receptor-binding specificity and pathogenicity in natural reassortant and non-reassortant h3n2 swine influenza virus.genetic reassortment between human and avian influenza viruses can create pandemic viruses. influenza surveillance of pigs in jilin province, in china during 2007-2008 revealed that there were two distinguishable genotypes: a human-like h3n2 genotype and a double-reassortant genotype derived from the human h3n2 and avian h5 viruses. in this study, viral infection potential, replication kinetics, and pathogenicity were compared. the solid-phase binding assay demonstrated that both viruses promine ...201424305615
a single amino acid substitution in the hemagglutinin of h3n2 subtype influenza a viruses is associated with resistance to the long pentraxin ptx3 and enhanced virulence in mice.the long pentraxin, pentraxin 3 (ptx3), can play beneficial or detrimental roles during infection and disease by modulating various aspects of the immune system. there is growing evidence to suggest that ptx3 can mediate antiviral activity in vitro and in vivo. previous studies demonstrated that ptx3 and the short pentraxin serum amyloid p express sialic acids that are recognized by the hemagglutinin (ha) glycoprotein of certain influenza a viruses (iav), resulting in virus neutralization and an ...201424307735
genetic characterization of seasonal influenza a (h3n2) viruses in ontario during 2010-2011 influenza season: high prevalence of mutations at antigenic sites.the direct effect of antigenic site mutations in influenza viruses on antigenic drift and vaccine effectiveness is poorly understood.201424313991
[selection pressure analysis of h3n2 influenza virus from china between 1992 and 2012].in order to investigate the relationship between selection pressure and the prevalence of antigenic clusters, we sequenced and analyzed the h3n2 influenza virus from china between 1992 and 2012.201324319949
egg- or cell culture-derived hemagglutinin mutations impair virus stability and antigen content of inactivated influenza vaccines.egg-derived viruses are the only available seed material for influenza vaccine production. vaccine manufacturing is done in embryonated chicken eggs, mdck or vero cells. in order to contribute to efficient production of influenza vaccines, we investigate whether the quality of inactivated vaccines is influenced by the propagation substrate. we demonstrate that h3n2 egg-derived seed viruses (a/brisbane/10/07, ivr147, and a/uruguay/716/07) triggered the hemagglutinin (ha) conformational change und ...201424323790
influenza a(h7n9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility.without baseline human immunity to the emergent avian influenza a(h7n9) virus, neuraminidase inhibitors are vital for controlling viral replication in severe infections. an amino acid change in the viral neuraminidase associated with drug resistance, na-r292k (n2 numbering), has been found in some h7n9 clinical isolates. here we assess the impact of the na-r292k substitution on antiviral sensitivity and viral replication, pathogenicity and transmissibility of h7n9 viruses. our data indicate that ...201324326875
comparative analysis of micrornas from the lungs and trachea of dogs (canis familiaris) infected with canine influenza virus.micrornas (mirnas) are a class of endogenous non-coding small rnas of 18-22-nucleotides in length that regulate gene expression at the post-transcriptional level. the objective of this study was to examine the differences in the mirna expression profiles of the lungs and trachea of beagle dogs infected with canine influenza virus (civ). total rna was isolated from lung and trachea tissues of beagle dogs infected and non-infected with h3n2 civ at 4 dpi. a total of 41,512,315 and 39,107,475 reads ...201424333372
a patient who survived primary seasonal influenza viral pneumonia: histologic findings obtained via bronchoscopy.the histological findings and clinical course of primary seasonal influenza viral pneumonia have not been fully elucidated. we herein report the case of a 65-year-old man with primary seasonal influenza viral pneumonia. the patient presented with fever, myalgia, general fatigue and dyspnea of seven days duration. chest computed tomography showed bilateral ground-glass opacity and consolidation. a rapid influenza virus antigen test was positive for influenza a virus. we diagnosed him as having co ...201324334588
a common solution to group 2 influenza virus neutralization.the discovery and characterization of broadly neutralizing antibodies (bnabs) against influenza viruses have raised hopes for the development of monoclonal antibody (mab)-based immunotherapy and the design of universal influenza vaccines. only one human bnab (cr8020) specifically recognizing group 2 influenza a viruses has been previously characterized that binds to a highly conserved epitope at the base of the hemagglutinin (ha) stem and has neutralizing activity against h3, h7, and h10 viruses ...201424335589
protective efficacy in mice of monovalent and trivalent live attenuated influenza vaccines in the background of cold-adapted a/x-31 and b/lee/40 donor strains.influenza virus continues to take a heavy toll on human health and vaccination remains the mainstay of efforts to reduce the clinical impact imposed by viral infections. proven successful for establishing live attenuated vaccine donor strains, cold-adapted live attenuated influenza vaccines (caivs) have become an attractive modality for controlling the virus infection. previously, we developed the cold-adapted strains a/x-31 and b/lee/40 as novel donor strains of caivs against influenza a and b ...201424342248
predicting the emergence of h3n2 influenza viruses reveals contrasted modes of evolution of ha and na antigens.vaccine design for rapidly changing viruses is based on empirical surveillance of strains circulating in a given season to assess those that will most likely spread during the next season. the choice of which strains to include in the vaccine is critical, as an erroneous decision can lead to a nonimmunized human population that will then be at risk in the face of an epidemic or, worse, a pandemic. here, we present the first steps toward a very general phylogenetic approach to predict the emergen ...201424343641
tmprss2 is essential for influenza h1n1 virus pathogenesis in mice.annual influenza epidemics and occasional pandemics pose a severe threat to human health. host cell factors required for viral spread but not for cellular survival are attractive targets for novel approaches to antiviral intervention. the cleavage activation of the influenza virus hemagglutinin (ha) by host cell proteases is essential for viral infectivity. however, it is unknown which proteases activate influenza viruses in mammals. several candidates have been identified in cell culture studie ...201324348248
phylodynamics of the emergence of influenza viruses after cross-species transmission.human populations are constantly exposed to emerging pathogens such as influenza a viruses that result from cross-species transmissions. generally these sporadic events are evolutionary dead-ends, but occasionally, viruses establish themselves in a new host that offers a novel genomic context to which the virus must adjust to avoid attenuation. however, the dynamics of this process are unknown. here we present a novel method to characterize the time it takes to g+c composition at third codon pos ...201324358190
influenza a virus infections in swine: pathogenesis and diagnosis.influenza has been recognized as a respiratory disease in swine since its first appearance concurrent with the 1918 "spanish flu" human pandemic. all influenza viruses of significance in swine are type a, subtype h1n1, h1n2, or h3n2 viruses. influenza viruses infect epithelial cells lining the surface of the respiratory tract, inducing prominent necrotizing bronchitis and bronchiolitis and variable interstitial pneumonia. cell death is due to direct virus infection and to insult directed by leuk ...201424363301
influenza associated mortality in southern china, 2010-2012.influenza caused substantial morbidity and mortality worldwide. the mortality burden caused by influenza has been under evaluation; however, data assessing this burden have been relatively sparse in tropical or subtropical regions. we estimated influenza-associated mortality in guangzhou, china and assessed the excess mortality due to different influenza virus subtypes.201424370709
genomewide analysis of reassortment and evolution of human influenza a(h3n2) viruses circulating between 1968 and 2011.influenza a(h3n2) viruses became widespread in humans during the 1968 h3n2 virus pandemic and have been a major cause of influenza epidemics ever since. these viruses evolve continuously by reassortment and genomic evolution. antigenic drift is the cause for the need to update influenza vaccines frequently. using two data sets that span the entire period of circulation of human influenza a(h3n2) viruses, it was shown that influenza a(h3n2) virus evolution can be mapped to 13 antigenic clusters. ...201424371052
h1n1, but not h3n2, influenza a virus infection protects ferrets from h5n1 encephalitis.seasonal influenza causes substantial morbidity and mortality because of efficient human-to-human spread. rarely, zoonotic strains of influenza virus spread to humans, where they have the potential to mediate new pandemics with high mortality. we studied systemic viral spread after intranasal infection with highly pathogenic avian influenza virus (h5n1 [a/viet nam/1203/2004]) in ferrets with or without prior pandemic h1n1pdm09 (a/mexico/4108/2009) or h3n2 (a/victoria/361/2011) infection. after i ...201324371072
genetic and antigenic typing of seasonal influenza virus breakthrough cases from a 2008-2009 vaccine efficacy trial.estimations of the effectiveness of vaccines against seasonal influenza virus are guided by comparisons of the antigenicities between influenza virus isolates from clinical breakthrough cases with strains included in a vaccine. this study examined whether the prediction of antigenicity using a sequence analysis of the hemagglutinin (ha) gene-encoded ha1 domain is a simpler alternative to using the conventional hemagglutination inhibition (hi) assay, which requires influenza virus culturing. spec ...201424371255
bifunctional thiosialosides inhibit influenza virus.we have synthesized a panel of bivalent s-sialoside analogues, with modifications at the 4 position, as inhibitors of influenza virus. these first generation compounds show ic50 values ranging from low micromolar to high nanomolar in enzyme inhibition and plaque reduction assays with two intact viruses, influenza h1n1 (a/california/07/2009) and h3n2 (a/hongkong/8/68).201424374271
severity of the two post-pandemic influenza seasons 2010-11 and 2011-12 in northern greece.since the pandemic in 2009, the two following post pandemic influenza seasons have been associated with increased morbidity and mortality rates in northern greece. the scope of this short report is to provide relevant epidemiological information, an evaluation of the efficacy of the seasonal vaccine and antiviral drugs. molecular analysis revealed the close match of a(h1n1) 2009 pandemic and post-pandemic 2010-11 viruses with the vaccine virus. however, a proportion of the influenza a(h3n2) and ...201324376321
a historical perspective of influenza a(h1n2) virus.the emergence and transition to pandemic status of the influenza a(h1n1)a(h1n1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. within a short time of the initial emergence of a(h1n1)pdm09 virus, novel reassortants were isolated from swine. in late 2011, a variant (v) h3n2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase wit ...201424377419
inferring the antigenic epitopes for highly pathogenic avian influenza h5n1 viruses.the evasion of influenza virus from host immune surveillance is mainly mediated through its surface protein hemagglutinin (ha), the main component of influenza vaccine. thus, identification of influenza virus antigenic epitopes on ha can not only help us understand the molecular mechanisms of viral immune escape but also facilitate vaccine strain selection. despite previous efforts, there is a lack of systematic definition of the antigenic epitopes for the highly pathogenic avian influenza (hpai ...201424380681
cyclic dipeptides from lactic acid bacteria inhibit proliferation of the influenza a virus.we isolated lactobacillus plantarum lbp-k10 from the traditional korean fermented food kimchi. when organic acids were removed, the culture filtrate of this isolate showed high antiviral activity (measured using a plaque-forming assay) against the influenza a (h3n2) virus. two fractions that were active against influenza a virus were purified from the culture filtrate using a c18 column with high-performance liquid chromatography. these active fractions were crystallized and identified to be the ...201324385362
recombinant porcine surfactant protein d inhibits influenza a virus replication ex vivo.influenza is a major burden to public health. due to high mutation rates and selection pressure, mutant viruses emerge which are resistant to currently used antiviral drugs. therefore, there is a need for the development of novel classes of antiviral drugs that suffer less from the emergence of resistant viruses. antiviral drugs based on collectin-like surfactant protein d (sp-d) may fulfil these requirements. especially porcine sp-d displays strong antiviral activity to influenza a viruses. in ...201424389095
identification of adaptive mutations in the influenza a virus non-structural 1 gene that increase cytoplasmic localization and differentially regulate host gene expression.the ns1 protein of influenza a virus (iav) is a multifunctional virulence factor. we have previously characterized gain-of-function mutations in the ns1 protein arising from the experimental adaptation of the human isolate a/hong kong/1/1968(h3n2) (hk) to the mouse. the majority of these mouse adapted ns1 mutations were demonstrated to increase virulence, viral fitness, and interferon antagonism, but differ in binding to the post-transcriptional processing factor cleavage and polyadenylation spe ...201324391972
immunogenicity of a 2009 pandemic influenza virus a h1n1 vaccine, administered simultaneously with the seasonal influenza vaccine, in children receiving chemotherapy.no examination of simultaneous vaccination against pandemic h1n1 and the seasonal influenza virus strains, in children with cancer receiving chemotherapy, are yet published. we investigated the immunogenicity of a whole-virion, inactivated, adjuvanted pandemic h1n1, and seasonal influenza vaccines administered simultaneously to children with cancer undergoing chemotherapy.201424395342
establishment of serological herd profiles for zoonoses and production diseases in pigs by "meat juice multi-serology".the most important pork-borne zoonotic diseases in humans such as salmonelloses and yersinioses cause only latent infections in pigs. thus, the infection of pigs does not result in apparent or palpable alterations in the pig carcasses. this is the major reason, why the traditional meat inspection with adspection, palpation and incision is not able to control the food safety risks of today. the objective of this paper is to evaluate a set of serological tests, which provides a classification of p ...201424411983
intrasubtype reassortments cause adaptive amino acid replacements in h3n2 influenza genes.reassortments and point mutations are two major contributors to diversity of influenza a virus; however, the link between these two processes is unclear. it has been suggested that reassortments provoke a temporary increase in the rate of amino acid changes as the viral proteins adapt to new genetic environment, but this phenomenon has not been studied systematically. here, we use a phylogenetic approach to infer the reassortment events between the 8 segments of influenza a h3n2 virus since its ...201424415946
evaluation of heterosubtypic cross-protection against highly pathogenic h5n1 by active infection with human seasonal influenza a virus or trivalent inactivated vaccine immunization in ferret models.the threat of highly pathogenic avian influenza (hpai) h5n1 viruses to cause the next pandemic remains a major concern. here, we evaluated the cross-protection induced by natural infection of human seasonal influenza strains or immunization with trivalent inactivated influenza vaccine (tiv) against hpai h5n1 (a/vietnam/1203/2004) virus in ferrets. groups were treated with pbs (group a), infected with h1n1 (group b) or h3n2 (group c) virus, or immunized with tiv (group d). twelve weeks after the ...201424421115
synthesis, structure and inhibitory activity of a stereoisomer of oseltamivir carboxylate.a stereodivergent plan is presented leading to all eight stereoisomers of oseltamivir carboxylate (oc). key chemical manoeuvers are (1) a three-component vinylogous mukaiyama-mannich reaction, which sets the whole carbon skeleton and heteroatom substituents, and (2) an intramolecular, silylative mukaiyama aldol reaction, which creates the targeted carbocycle. the viability of the plan was demonstrated by the first total synthesis of 4-epi-oseltamivir carboxylate (6), accessed in 15 steps from gl ...201424425043
mechanism of a decrease in potency for the recombinant influenza a virus hemagglutinin h3 antigen during storage.the recombinant hemagglutinin (rha)-based influenza vaccine flublok® has recently been approved in the united states as an alternative to the traditional egg-derived flu vaccines. flublok is a purified vaccine with a hemagglutinin content that is threefold higher than standard inactivated influenza vaccines. when rha derived from an h3n2 influenza virus was expressed, purified, and stored for 1 month, a rapid loss of in vitro potency (∼50%) was observed as measured by the single radial immunodif ...201424425059
serum 25-hydroxyvitamin d level and influenza vaccine immunogenicity in children and adolescents.vaccination is an important strategy in the prevention of influenza, but immunologic response to vaccination can vary widely. recent studies have shown an association between serum 25-hydroxyvitamin d (25[oh]d) levels and immune function. the purpose of this study was to determine if serum 25(oh)d level correlates with influenza vaccine immunogenicity in children and adolescents.201424427274
novel oral anti-influenza prodrug candidate av5075s.development of a novel drug candidate with improved activity against influenza virus neuraminidase (na) compared with currently available therapeutics.201424428978
repetitive fulminant influenza myocarditis requiring the use of circulatory assist devices.a 52-year-old man was admitted to our hospital due to shortness of breath that developed one week after the diagnosis of influenza infection. he had a past history of myocarditis associated with influenza b infection 16 years before the current admission. the patient's left ventricular function showed diffuse hypokinesis with a left ventricular ejection fraction of 28%. due to the progression of heart failure, the infusion of catecholamines and insertion of an intra-aortic balloon pump were requ ...201424429449
structural insights into the membrane fusion mechanism mediated by influenza virus hemagglutinin.membrane fusion is involved in many fundamental cellular processes and entry of enveloped viruses into host cells. influenza type a virus ha has long served as a paradigm for mechanistic studies of protein-mediated membrane fusion via large-scale structural rearrangements induced by acidic ph. here we report the newly determined crystal structure of influenza b virus ha2 in the postfusion state. together with a large number of previously determined prefusion structures of influenza a and b virus ...201424433110
evidence for a crucial role of a host non-coding rna in influenza a virus replication.a growing body of evidence suggests the non-protein coding human genome is of vital importance for human cell function. besides small rnas, the diverse class of long non-coding rnas (lncrnas) recently came into focus. however, their relevance for infection, a major evolutionary driving force, remains elusive. using two commercially available microarray systems, namely ncode™ and sureprint™ g3, we identified differential expression of 42 ncrnas during influenza a virus (iav) infection in human lu ...201324440876
antiviral susceptibility of variant influenza a(h3n2)v viruses isolated in the united states from 2011 to 2013.since 2011, outbreaks caused by influenza a(h3n2) variant [a(h3n2)v] viruses have become a public health concern in the united states. the a(h3n2)v viruses share the a(h1n1)pdm09 m gene containing the marker of m2 blocker resistance, s31n, but do not contain any known molecular markers associated with resistance to neuraminidase (na) inhibitors (nais). using a fluorescent na inhibition (ni) assay, the susceptibilities of recovered a(h3n2)v viruses (n=168) to fda-approved (oseltamivir and zanamiv ...201424449767
epidemiological analysis of influenza a infection in cambodian pigs and recommendations for surveillance strategies.this study analysed the available data of seroprevalence to human influenza viruses in pigs in cambodia using generalized linear mixed models in order to improve understanding of factors underlying the spread of human influenza viruses in cambodian pigs. the associations between seroprevalence against seasonal h1n1 influenza virus in pigs and the population density of humans and pigs were not significant. however, a positive association between anti-h3 antibodies in pigs and the human population ...201524460959
genetic characterization of influenza a viruses circulating in pigs and isolated in north-east spain during the period 2006-2007.swine influenza virus is one of the most important pathogens involved in the swine respiratory disease complex. recent serological surveys showed a high prevalence of swine influenza strains belonging to the h1n1, h1n2 and h3n2 subtypes circulating in pigs in spain. however, little is known about their genome sequence. five swine influenza strains were isolated from some unrelated outbreaks occurred during 2006-2007, and their complete genome sequences were determined. phylogenetic analysis reve ...201424461956
predictability of antigenic evolution for h3n2 human influenza a virus.influenza a virus continues to pose a threat to public health. since this virus can evolve escape mutants rapidly, it is desirable to predict the antigenic evolution for developing effective vaccines. although empirical methods have been proposed and reported to predict the antigenic evolution more or less accurately, they did not provide much insight into the effects of unobserved mutations and the mechanisms of antigenic evolution. here a theoretical method was introduced to predict the antige ...201324463525
intranasal vaccination promotes detrimental th17-mediated immunity against influenza infection.influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. we evaluated the efficacy of a synthetic toll-like receptor 4 agonist crx-601 as an adjuvant for enhancing vaccine-induced protection against influenza infectio ...201424465206
the duration of fever and other symptoms after the initiation of laninamivir octanoate hydrate in the japanese 2011-2012 influenza season.laninamivir octanoate hydrate (laninamivir) is a long-acting, single inhalation neuraminidase inhibitor that was approved in japan in 2010 for the treatment of influenza a and b virus infection. we investigated the duration of fever and other symptoms after the initiation of laninamivir in the japanese 2011-2012 influenza season. virus isolation was done and the 50% inhibitory concentration (ic₅₀) was measured for the virus isolates at days 1 and 5. for 211 patients (a(h3n2): 190, b: 21), the me ...201424486167
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