Publications

TitleAbstractYear
Filter
PMID(sorted descending)
Filter
modelling of seasonal influenza and estimation of the burden in tunisia.the burden of influenza was estimated from surveillance data in tunisia using epidemiological parameters of transmission with who classical tools and mathematical modelling. the incidence rates of influenza-associated influenza-like illness (ili) per 100 000 were 18 735 in 2012/2013 season; 5536 in 2013/14 and 12 602 in 2014/15. the estimated proportions of influenza-associated ili in the total outpatient load were 3.16%; 0.86% and 1.98% in the 3 seasons respectively. distribution of influenza v ...201627714740
detection of influenza b viruses with reduced sensitivity to neuraminidase inhibitor in morocco during 2014/15 season.we monitored phenotypic and genotypic susceptibility of influenza viruses circulating in morocco during 2014-2015 to oseltamivir and zanamivir. throat and nasal swab specimens were collected from outpatients (with influenza-like illness) and inpatients (with severe acute respiratory illness) and tested for influenza viruses using real-time reverse transcription polymerase chain reaction. positive samples were inoculated in mdck cells and virus phenotypic susceptibility to neuraminidase inhibitor ...201627714739
characteristics of severe acute respiratory infectionassociated hospitalization in yemen, 2014/15.this study aims to describe etiological agents, demographic details of patients, seasonality and underlying conditions among patients hospitalized due to viral severe acute respiratory infection (sari) in yemen. we carried out a retrospective descriptive analysis of data from january 2014 to december 2015. nasopharyngeal swabs were taken from each patient for laboratory testing. a total of 1346 diagnostic specimens were tested, of which 733 (54%) were positive for influenza viruses. influenza a( ...201627714737
sequence amplification via cell passaging creates spurious signals of positive adaptation in influenza virus h3n2 hemagglutinin.clinical influenza a virus isolates are frequently not sequenced directly. instead, a majority of these isolates (~70% in 2015) are first subjected to passaging for amplification, most commonly in non-human cell culture. here, we find that this passaging leaves distinct signals of adaptation, which can confound evolutionary analyses of the viral sequences. we find distinct patterns of adaptation to madin-darby (mdck) and monkey cell culture absent from unpassaged hemagglutinin sequences. these p ...201627713835
deep sequencing of influenza a virus from a human challenge study reveals a selective bottleneck and only limited intrahost genetic diversification.knowledge of influenza virus evolution at the point of transmission and at the intrahost level remains limited, particularly for human hosts. here, we analyze a unique viral data set of next-generation sequencing (ngs) samples generated from a human influenza challenge study wherein 17 healthy subjects were inoculated with cell- and egg-passaged virus. nasal wash samples collected from 7 of these subjects were successfully deep sequenced. from these, we characterized changes in the subjects' vir ...201627707932
constitutively expressed ifitm3 protein in human endothelial cells poses an early infection block to human influenza viruses.a role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. as the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. we found that a subset of avian influenza viruses, including potentially pandemic h5n1, h7n9, and h9n2 viruses, could infect huma ...201627707929
2014-2015 influenza vaccine effectiveness in the united states by vaccine type.circulating a/h3n2 influenza viruses drifted significantly after strain selection for the 2014-2015 vaccines. also in 2014-2015, the advisory committee on immunization practices recommended preferential use of live attenuated influenza vaccine (laiv) over inactivated influenza vaccine (iiv) among children aged 2-8 years.201627702768
viral inhibition of bacterial phagocytosis by human macrophages: redundant role of cd36.macrophages are essential to maintaining lung homoeostasis and recent work has demonstrated that influenza-infected lung macrophages downregulate their expression of the scavenger receptor cd36. this receptor has also been shown to be involved in phagocytosis of streptococcus pneumoniae, a primary agent associated with pneumonia secondary to viral infection. the aim of this study was to investigate the role of cd36 in the effects of viral infection on macrophage phagocytic function. human monocy ...201627701435
an early innate response underlies severe influenza-induced exacerbations of asthma in a novel steroid-insensitive and anti-il-5-responsive mouse model.acute worsening of asthma symptoms (exacerbation) is predominantly triggered by respiratory viruses, with influenza causing the most severe exacerbations. the lack of an adequate animal model hampers mechanistic insight and the development of new therapeutics.201727696462
genetic characterization of influenza viruses from influenza-related hospital admissions in the st. petersburg and valencia sites of the global influenza hospital surveillance network during the 2013/14 influenza season.continuous surveillance for genetic changes in circulating influenza viruses is needed to guide influenza prevention and control.201627690141
immunity against influenza a(h1n1) infections is determined by age at the time of initial strain circulation.we explored age-dependent patterns in haemagglutination inhibition (hi) titre to seasonal [1956 a(h1n1), 1977 a(h1n1), 2007 a(h1n1)] and pandemic [a(h1n1)pdm09] influenza strains using serological data collected from an adult french influenza cohort. subjects were recruited by their general practitioners from 2008 to 2009 and followed until 2010. we explored age-related differences between strain-specific hi titres using 1053 serological samples collected over the study period from 398 unvaccina ...201727682472
introduction, evolution, and dissemination of influenza a viruses in exhibition swine in the united states during 2009 to 2013.the swine-human interface created at agricultural fairs, along with the generation of and maintenance of influenza a virus diversity in exhibition swine, presents an ongoing threat to public health. nucleotide sequences of influenza a virus isolates collected from exhibition swine in ohio (n = 262) and indiana (n = 103) during 2009 to 2013 were used to investigate viral evolution and movement within this niche sector of the swine industry. phylogenetic and bayesian analyses were employed to iden ...201627681134
antiviral spirotriscoumarins a and b: two pairs of oligomeric coumarin enantiomers with a spirodienone-sesquiterpene skeleton from toddalia asiatica.two pairs of oligomeric coumarin enantiomers, spirotriscoumarin a [(+)-1 and (-)-1] and spirotriscoumarin b [(+)-2 and (-)-2], with a spirodienone-sesquiterpene fused skeleton were isolated from toddalia asiatica. their structures were unambiguously established using spectroscopic data, x-ray diffraction analysis, and the electronic circular dichroism (ecd) method. the racemic mixtures (±)-1 and (±)-2 exhibit 3-to-6-fold stronger antiviral activity against influenza virus a (h3n2) (ic50: 3.13 an ...201627673343
canine h3n8 influenza vaccines partially protect mice against the canine h3n2 strain currently circulating in the united states.influenza a viruses infect many species and cross-species transmission occurs occasionally. an equine h3n8 influenza virus began circulating in dogs in 1999 and an avian h3n2 influenza virus began circulating in dogs in 2006. the canine h3n8 (ch3n8) viral strain has become endemic in parts of the united states and there is a commercially available vaccine against this strain. the canine h3n2 (ch3n2) strain did not circulate widely in the united states until 2015. here, we used a mouse model to d ...201627670073
sensitive detection and simultaneous discrimination of influenza a and b viruses in nasopharyngeal swabs in a single assay using next-generation sequencing-based diagnostics.reassortment of 2009 (h1n1) pandemic influenza virus (pdh1n1) with other strains may produce more virulent and pathogenic forms, detection and their rapid characterization is critical. in this study, we reported a "one-size-fits-all" approach using a next-generation sequencing (ngs) detection platform to extensively identify influenza viral genomes for diagnosis and determination of novel virulence and drug resistance markers. a de novo module and other bioinformatics tools were used to generate ...201727658193
update: influenza activity - united states and worldwide, may 22-september 10, 2016.during may 22-september 10, 2016,* the united states experienced typical low levels of seasonal influenza activity overall; beginning in late august, clinical laboratories reported a slight increase in influenza positive test results and cdc received reports of a small number of localized influenza outbreaks caused by influenza a (h3n2) viruses. influenza a (h1n1)pdm09, influenza a (h3n2), and influenza b viruses were detected during may-september in the united states and worldwide. the majority ...201627657671
functionalized magnetic microparticle-based colorimetric platform for influenza a virus detection.a colorimetric platform for influenza a virus detection was developed by using the high efficiency of enzymatic catalysis and the reduction of gold ions with hydrogen peroxide. aptamer-functionalized magnetic microparticles were synthesized to capture the influenza a virus. this was followed by the binding of cona-gox-aunps to the h3n2 virus through the cona-glycan interaction. the sandwich complex was subsequently dispersed in glucose solution to trigger an enzymatic reaction to produce hydroge ...201627655150
reassortment of high-yield influenza viruses in vero cells and safety assessment as candidate vaccine strains.vaccination is the practiced and accessible measure for preventing influenza infection. because chicken embryos used for vaccine production have various insufficiencies, more efficient methods are needed. african green monkey kidney (vero) cells are recommended by the world health organization (who) as a safe substitute for influenza vaccine production for humans. however, the influenza virus usually had low-yield in vero cells, which limits the usage of vero cellular vaccines. this study used 2 ...201727648636
influenza in children.in children, influenza is one among the commonest causes of acute respiratory illness and loss of school days. influenza a, b, and c are 3 types of viruses responsible for illness. type a virus has many subtypes based on antigens but type b and type c viruses have no known subtypes. currently, influenza a/h1n1, a/h3n2, and influenza type b viruses are circulating in humans. transmission of influenza occurs through droplets from infected person or through direct contact with person or fomites. cl ...201727641976
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
long-term adaptation of the influenza a virus by escaping cytotoxic t-cell recognition.the evolutionary adaptation of the influenza a virus (iav) to human antibodies is well characterised. much less is known about the long-term evolution of cytotoxic t lymphocyte (ctl) epitopes, which are important antigens for clearance of infection. we construct an antigenic map of iavs of all human subtypes using a compendium of 142 confirmed ctl epitopes, and show that iav evolved gradually in the period 1932-2015, with infrequent antigenic jumps in the h3n2 subtype. intriguingly, the number o ...201627629812
dynamic convergent evolution drives the passage adaptation across 48 years' history of h3n2 influenza evolution.influenza viruses are often propagated in a diverse set of culturing media and additional substitutions known as passage adaptation can cause extra evolution in the target strain, leading to ineffective vaccines. using 25,482 h3n2 ha1 sequences curated from global initiative on sharing all influenza data and national center for biotechnology information databases, we found that passage adaptation is a very dynamic process that changes over time and evolves in a seesaw like pattern. after crossin ...201627604224
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
virologic differences do not fully explain the diversification of swine influenza viruses in the united states.influenza a(h1n1) viruses entered the u.s. swine population following the 1918 pandemic and remained genetically stable for roughly 80 years. in 1998, there was an outbreak of influenza-like illness among swine that was caused by a(h3n2) viruses containing the triple reassortant internal gene (trig) cassette. following the trig cassette emergence, numerous reassortant viruses were isolated in nature, suggesting that the trig virus had an enhanced ability to reassort compared to the classical swi ...201627581984
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
primer development to obtain complete coding sequence of ha and na genes of influenza a/h3n2 virus.influenza is an acute respiratory illness and has become a serious public health problem worldwide. the need to study the ha and na genes in influenza a virus is essential since these genes frequently undergo mutations. this study describes the development of primer sets for rt-pcr to obtain complete coding sequence of hemagglutinin (ha) and neuraminidase (na) genes of influenza a/h3n2 virus from indonesia. the primers were developed based on influenza a/h3n2 sequence worldwide from global initi ...201627576569
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
seasonal influenza vaccination of children induces humoral and cell-mediated immunity beyond the current season: cross-reactivity with past and future strains.influenza viruses gradually accumulate point mutations, reducing the effectiveness of prior immune protection.201627571905
phenotypic and genotypic analysis of influenza viruses isolated from adult subjects during a phase ii study of intravenous zanamivir in hospitalised subjects.intravenous zanamivir (ivz) is a neuraminidase (na) inhibitor (nai) under investigation for the treatment of subjects hospitalised with influenza. the study included 130 symptomatic, hospitalised adults with influenza. subjects received ivz for 5-10 days. viruses were cultured and analysed for susceptibility to zanamivir. mean ic50s (n = 50) (±sd) for influenza a/h1n1pdm09, a/h3n2 and influenza b were 0.20 ± 0.06, 0.26 ± 0.07 and 1.61 ± 0.35 nm, respectively, and are comparable to data observed ...201627568923
influenza-like illness outbreaks in nursing homes in corsica, france, 2014-2015: epidemiological and molecular characterization.to study the molecular epidemiology of the influenza outbreaks in nursing homes (nhs) to determine whether multiple influenza strains were involved.201627563533
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
cell-mediated immunity against antigenically drifted influenza a(h3n2) viruses in children during a vaccine mismatch season.emergence of antigenically drifted influenza a(h3n2) viruses resulted in reduced vaccine effectiveness in all age groups during the 2014-2015 influenza season. in children, inactivated influenza vaccine (iiv) elicited neutralizing antibodies (abs) against drifted strains at significantly lower levels than against the vaccine strain. little is known about the cross-reactivity of cell-mediated immunity against drifted strains in children.201627534687
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
[mutations in the neuraminidase gene of the epidemic influenza virus strain isolated in the 2012-2013 season and improvement of a pcr assay for the detection of influenza virus].in 2011, we developed a real-time rt-pcr method to rapidly and sensitively detect three subtypes of influenza a virus [h1n1, h3n2, and influenza (h1n1) 2009] and influenza b virus (the conventional pcr method). this method was useful during the 2011-2012 epidemic season. however, epidemic influenza a virus strain h3n2 in the 2012-2013 season was undetectable by this method, possibly due to mutation in the neuraminidase (na) gene of epidemic influenza a virus strain h3n2. therefore, we improved t ...201427526538
[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
evaluation of a set of c9 n-acyl neu5ac2en mimetics as viral sialidase selective inhibitors.identification of selective influenza viral sialidase inhibitors is highly desirable in order to minimize or avoid the adverse effects due to the possible inhibition of endogenous human sialidases. we recently reported the evaluation of c9 n-acyl neu5ac2en mimetics as probes for human sialidases. herein, we describe the in vitro activity of the same set of c9 n-acyl neu5ac2en mimetics against sialidases expressed by influenza virus a/pr/8/34 (h1n1), a/memphis/1/72 (h3n2), and a/duck/313/78 (h5n3 ...201127525119
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
[prevalence characteristics of influenza viruses in children in beijing during 2014-2015 and 2015-2016 influenza seasons].to compare the prevalence characteristics of influenza viruses in children in beijing during 2014-2015 and 2015-2016 influenza seasons.201627510869
incorporating structure context of ha protein to improve antigenicity calculation for influenza virus a/h3n2.the rapid and consistent mutation of influenza requires frequent evaluation of antigenicity variation among newly emerged strains, during which several in-silico methods have been reported to facilitate the assays. in this paper, we designed a structure-based antigenicity scoring model instead of those sequence-based previously published. protein structural context was adopted to derive the antigenicity-dominant positions, as well as the physic-chemical change of local micro-environment in corre ...201627498613
immunogenicity and protective efficacy of recombinant fusion proteins containing spike protein of infectious bronchitis virus and hemagglutinin of h3n2 influenza virus in chickens.infectious bronchitis (ib) is an acute and highly contagious viral respiratory disease of chickens and vaccination is the main method for disease control. the s1 protein, which contains several virus neutralization epitopes, is considered to be a target site of vaccine development. however, although protective immune responses could be induced by recombinant s1 protein, the protection rate in chickens was still low (<50%). here, we generated fused s1 proteins with ha2 protein (rs1-ha2) or transm ...201627497621
influenza virus vaccine for neglected hosts: horses and dogs.this study provides information regarding vaccine research and the epidemiology of influenza virus in neglected hosts (horses and dogs). equine influenza virus (eiv) causes a highly contagious disease in horses and other equids, and outbreaks have occurred worldwide. eiv has resulted in costly damage to the horse industry and has the ability of cross the host species barrier from horses to dogs. canine influenza is a virus of equine or avian origin and infects companion animals that live in clos ...201627489801
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
population genetic processes affecting the mode of selective sweeps and effective population size in influenza virus h3n2.human influenza virus a/h3n2 undergoes rapid adaptive evolution in response to host immunity. positively selected amino acid substitutions have been detected mainly in the hemagglutinin (ha) segment. the genealogical tree of ha sequences sampled over several decades comprises a long trunk and short side branches, which indicates small effective population size. various studies have reproduced this unique genealogical structure by modeling recurrent positive selection. however, it has not been cl ...201627487769
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
influenza a virus in backyard pigs and poultry in rural cambodia.surveillance of influenza virus in humans and livestock is critical, given the worldwide public health threats and livestock production losses. livestock farming involving close proximity between humans, pigs and poultry is often practised by smallholders in low-income countries and is considered an important driver of influenza virus evolution. this study determined the prevalence and genetic characteristics of influenza a virus (iav) in backyard pigs and poultry in cambodia. a total of 751 ani ...201627484711
recognition of influenza h3n2 variant virus by human neutralizing antibodies.since 2011, over 300 human cases of infection, especially in exposed children, with the influenza a h3n2 variant (h3n2v) virus that circulates in swine in the us have been reported. the structural and genetic basis for the lack of protection against h3n2v induced by vaccines containing seasonal h3n2 antigens is poorly understood. we isolated 17 human monoclonal antibodies (mabs) that neutralized h3n2v virus from subjects experimentally immunized with an h3n2v candidate vaccine. six mabs exhibite ...201627482543
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
molecular and antigenic characterization of the h3 hemagglutinin of h3n2 influenza a virus strains collected in the czech republic during the 2014/2015 epidemic season.the 2014/2015 influenza epidemic season was characterized by the predominance of the h3n2 subtype. the presented study investigated the genetic and antigenic heterogeneity of the h3n2 strains collected in the czech republic from november 2014 to march 2015. phylogenetic analysis of the representative h3 hemagglutinin sequences was performed and the glycosylation status and crucial antigenic mutations were compared relative to the 2014 and 2015 vaccine strains (a/texas/50/2012 and a/switzerland/9 ...201727467326
clinical characteristics and factors associated with severe acute respiratory infection and influenza among children in jingzhou, china.influenza is an important cause of respiratory illness in children, but data are limited on hospitalized children with laboratory-confirmed influenza in china.201727465959
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
oseltamivir resistance in an influenza a (h3n2) virus isolated from an immunocompromised patient during the 2014-2015 influenza season in alberta, canada.this manuscript describes the identification of an oseltamivir-resistant influenza a (h3n2) virus in a respiratory specimen collected from an immunocompromised patient in alberta, canada, during the 2014-2015 influenza season. following treatment with oseltamivir, neuraminidase (na) gene sequencing indicated the presence of an r292k mutation. phenotypic susceptibility testing by the na-star assay indicated a highly reduced inhibition by oseltamivir and normal inhibition by zanamivir. the use of ...201627442795
hospital surveillance of influenza strains: a concordant image of viruses identified by the swiss sentinel system?the swiss sentinel system for influenza virus surveillance reports influenza-like illness in the community through a network of primary care practitioners, but the epidemiologic, demographic, and virological characterization may differ from that observed in hospitalized patients with influenza.201727441401
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
seroepidemiological evidence of subtype h3n8 influenza virus infection among pet dogs in china.the h3n8 virus and the h3n2 virus are the main subtypes of canine influenza virus (civ). h3n8 civ mainly circulates in america, and h3n2 civ mainly circulates in asia. however, there was an outbreak of the asian h3n2 virus in the united states (us) in 2015. thus, it is important to evaluate the presence of subtype h3n8 virus in dogs in china. from may 2015 to november 2015, 600 sera from pet dogs were collected from guangzhou, shanghai, beijing and shenzhen for hemagglutination inhibition (hi) a ...201627414031
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
persistent infection of drug-resistant influenza a virus during chemotherapy for malignant lymphoma.we herein report the case of an 80-year-old man with malignant lymphoma who became persistently infected with influenza a virus. although he was repeatedly treated with na inhibitors, such as oseltamivir or peramivir, nasal cavity swab tests for influenza a antigen continued to be positive for more than 2 months. virological analyses revealed that he was infected with the na inhibitor-resistant a (h3n2) virus possessing an r292k substitution in the na protein. these findings suggest that a drug- ...201627374689
influenza vaccine effectiveness against antigenically drifted influenza higher than expected in hospitalized adults: 2014-2015.the 2014-2015 influenza season was severe, with circulating influenza a (h3n2) viruses that were antigenically drifted from the vaccine virus. reported vaccine effectiveness (ve) estimates from ambulatory care settings were markedly decreased.201627369320
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
[preparation and detection of anti-influenza a virus polymerase basic protein 1 polyclonal antibody].influenza a virus is an enveloped virus that belongs to the orthomyxoviridae family. it has 8 negative rna segments that encode 16 viral proteins. the viral polymerase consists of 3 proteins (pb 1, pb2 and pa) which plays an important role in the transcription and replication of the influenza a virus. polymerase basic protein 1 (pb 1) is a critical member of viral polymerase complex. in order to further study the function of pb1, we need to prepare the pb1 antibody with good quality. therefore, ...201627363203
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
in vitro neuraminidase inhibitory concentration (ic50) of four neuraminidase inhibitors against clinical isolates of the influenza viruses circulating in the 2010-2011 to 2014-2015 japanese influenza seasons.to assess the extent of viral resistance to the four neuraminidase inhibitors (nais), we measured their 50% inhibitory concentration (ic50) for influenza virus isolates from the 2014-2015 influenza season for comparison with those circulating in the 2010-2011 to 2013-2014 influenza seasons. viral isolation was done with specimens obtained prior to treatment, and the type and subtype of influenza was determined by rt-pcr using type- and subtype-specific primers. the ic50 was determined by a neura ...201627346379
combination activity of neuraminidase inhibitor oseltamivir and α-tocopherol in influenza virus a (h3n2) infection in mice.influenza is a highly contagious viral infection of the respiratory system. to attack two processes involved in flu pathogenesis-viral replication in the infected body and oxidative damages, we studied the combination effect of neuraminidase inhibitor oseltamivir and antioxidant α-tocopherol in experimental model of influenza.201527341844
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
il-2 and il-6 cooperate to enhance the generation of influenza-specific cd8 t cells responding to live influenza virus in aged mice and humans.an age-related decline in cytolytic activity has been described in cd8+ t cells and we have previously shown that the poor cd8+ effector t cell responses to influenza a/h3n2 challenge result from a decline in the proportion and function of these cytolytic t lymphocytes (ctl). here, we describe that addition of exogenous cytokines to influenza-stimulated pbmc from both aged mice and humans, enhances the generation of influenza specific cd8 ctl by increasing their proliferation and survival. our d ...201627322555
antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir.favipiravir, a viral rna-dependent rna polymerase inhibitor, has recently been approved in japan for influenza pandemic preparedness. here, we conducted a cell-based screening system to evaluate the susceptibility of influenza viruses to favipiravir. in this assay, the antiviral activity of favipiravir is determined by inhibition of virus-induced cytopathic effect, which can be measured by using a colorimetric cell proliferation assay. to demonstrate the robustness of the assay, we compared the ...201627321665
influenza a virus drift variants reduced the detection sensitivity of a commercial multiplex nucleic acid amplification assay in the season 2014/15.the influenza season 2014/15 was dominated by drift variants of influenza a(h3n2), which resulted in a reduced vaccine effectiveness. it was not clear if the performance of commercial nucleic-acid-based amplification (nat) assays for the detection of influenza was affected. the purpose of this study was to perform a real-life evaluation of two commercial nat assays. during january-april 2015, we tested a total of 665 samples from patients with influenza-like illness using the fast track diagnost ...201627316440
peripheral leukocyte migration in ferrets in response to infection with seasonal influenza virus.in order to better understand inflammation associated with influenza virus infection, we measured cell trafficking, via flow cytometry, to various tissues in the ferret model following infection with an a(h3n2) human seasonal influenza virus (a/perth/16/2009). changes in immune cells were observed in the blood, bronchoalveolar lavage fluid, and spleen, as well as lymph nodes associated with the site of infection or distant from the respiratory system. nevertheless clinical symptoms were mild, wi ...201627315117
historical and recent cases of h3 influenza a virus in turkeys in minnesota.subtype h3 influenza a viruses (iavs) are abundant in wild waterfowl and also infect humans, pigs, horses, dogs, and seals. in minnesota, turkeys are important and frequent hosts of iav from wild waterfowl and from pigs. over 48 yr of surveillance history, 11 hemagglutinin (ha) subtypes of iav from waterfowl, as well as two ha subtypes from swine, h1 and h3, have infected turkeys in minnesota. however, there have only been two cases of avian-origin h3 iav infections in turkeys during this 48-yr ...201627309087
effectiveness of the 2013 and 2014 southern hemisphere influenza vaccines against laboratory-confirmed influenza in young children using a test-negative design, bangkok, thailand.the thai advisory committee on immunization practices recommends annual influenza vaccination for children 6 months through 2 years of age, although older children may be vaccinated on request. we evaluated the effectiveness of the 2013 and 2014 inactivated influenza vaccines to reduce medically attended, laboratory-confirmed influenza illness among thai children aged 7-60 months.201627307102
influenza activity - united states, 2015-16 season and composition of the 2016-17 influenza vaccine.during the 2015-16 influenza season (october 4, 2015-may 21, 2016) in the united states, influenza activity* was lower and peaked later compared with the previous three seasons (2012-13, 2013-14, and 2014-15). activity remained low from october 2015 until late december 2015 and peaked in mid-march 2016. during the most recent 18 influenza seasons (including this season), only two other seasons have peaked in march (2011-12 and 2005-06). overall influenza activity was moderate this season, with a ...201627281364
correction: accelerating influenza research: vaccines, antivirals, immunomodulators and monoclonal antibodies. the manufacture of a new wild-type h3n2 virus for the human viral challenge model.[this corrects the article doi: 10.1371/journal.pone.0145902.].201727280602
effects of previous episodes of influenza and vaccination in preventing laboratory-confirmed influenza in navarre, spain, 2013/14 season.we estimated whether previous episodes of influenza and trivalent influenza vaccination prevented laboratory-confirmed influenza in navarre, spain, in season 2013/14. patients with medically-attended influenza-like illness (ma-ili) in hospitals (n = 645) and primary healthcare (n = 525) were included. we compared 589 influenza cases and 581 negative controls. ma-ili related to a specific virus subtype in the previous five seasons was defined as a laboratory-confirmed influenza infection with the ...201627277013
phylodynamics of influenza a(h3n2) in south america, 1999-2012.the limited influenza a(h3n2) genetic data available from the southern hemisphere (particularly from africa and latin america), constrains the accurate reconstruction of viral dissemination dynamics within those regions. our objective was to describe the spatial dissemination dynamics of influenza a(h3n2) within south america. a total of 469 sequences of the ha1 portion of the hemagglutinin gene (ha) from influenza a(h3n2) viruses sampled in temperate and tropical south american countries betwee ...201627275847
the human antimicrobial protein bactericidal/permeability-increasing protein (bpi) inhibits the infectivity of influenza a virus.in addition to their well-known antibacterial activity some antimicrobial peptides and proteins (amps) display also antiviral effects. a 27 aa peptide from the n-terminal part of human bactericidal/permeability-increasing protein (bpi) previously shown to harbour antibacterial activity inhibits the infectivity of multiple influenza a virus strains (h1n1, h3n2 and h5n1) the causing agent of the influenza pneumonia. in contrast, the homologous murine bpi-peptide did not show activity against influ ...201627273104
a novel small-molecule compound disrupts influenza a virus pb2 cap-binding and inhibits viral replication.the conserved residues 318-483 in the pb2 subunit of influenza a polymerase is an independently folded cap-binding domain (pb2cap) that exhibits a distinct binding mode from other host cap-binding proteins, which suggests that pb2cap might be an ideal drug target. this study aimed to identify a new class of anti-influenza inhibitors that specifically disrupts the interaction between pb2cap and host cap structures.201627272726
phylogenetic analysis and pathogenicity of h3 subtype avian influenza viruses isolated from live poultry markets in china.h3 subtype influenza a virus is one of the main subtypes that threats both public and animal health. however, the evolution and pathogenicity of h3 avian influenza virus (aiv) circulating in domestic birds in china remain largely unclear. in this study, seven h3 aivs (four h3n2 and three h3n8) were isolated from poultry in live poultry market (lpm) in china. phylogenetic analyses of full genomes showed that all viruses were clustered into eurasian lineage, except n8 genes of two h3n8 isolates fe ...201627270298
global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2014-2015.the world health organization (who) collaborating centres for reference and research on influenza (who ccs) tested 13,312 viruses collected by who recognized national influenza centres between may 2014 and may 2015 to determine 50% inhibitory concentration (ic50) data for neuraminidase inhibitors (nais) oseltamivir, zanamivir, peramivir and laninamivir. ninety-four per cent of the viruses tested by the who ccs were from three who regions: western pacific, the americas and europe. approximately 0 ...201627265623
mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.immunomodulators have been shown to improve the outcome of severe pneumonia. we have previously shown that mycophenolic acid (mpa), an immunomodulator, has antiviral activity against influenza a/wsn/1933(h1n1) using a high-throughput chemical screening assay. this study further investigated the antiviral activity and mechanism of action of mpa against contemporary clinical isolates of influenza a and b viruses. the 50 % cellular cytotoxicity (cc50) of mpa in madin darby canine kidney cell line w ...201627259985
canine influenza virus coinfection with staphylococcus pseudintermedius enhances bacterial colonization, virus load and clinical presentation in mice.canine influenza virus (civ) and staphylococcus pseudintermedius (sp) are pathogens that cause respiratory disease in dogs. considering bacterial infections following influenza are a leading cause of illness and death, it is of particular meaning to investigate the interaction between these two pathogens. in this study, balb/c mice were used as a mouse model to assess whether inoculation with civ h3n2 followed by s. pseudintermedius 72 h later resulted in exacerbation of disease. disease was cha ...201627259293
Displaying items 201 - 300 of 4452