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predicting clinical severity based on substitutions near epitope a of influenza a/h3n2.epitopes are the main targets for specific antibodies in the host defense systems. recent studies have shown that amino acid (aa) substitutions located within the influenza a/h3n2 hemagglutinin 1 (ha1) epitopes a-e, particularly in a and b, result in antigenic drift. viruses with such drift mutations may have resulted in more severe influenza-related illness during influenza epidemics between late 2012 and early 2015. we sought to quantify vaccine mismatches in epitopes a-e of the ha1 protein, a ...201526118307
antiviral glycosidic bisindole alkaloids from the roots of isatis indigotica.seven new glycosidic bisindole alkaloids, isatindigobisindolosides a-g (1-7), were isolated from an aqueous extract of the isatis indigotica roots. their structures including absolute configurations were determined by spectroscopic and chemical methods, together with calculations of electronic circular dichroism (ecd) spectra based on the quantum-mechanical time-dependent density functional theory. in the nmr spectra of 1-3, it is found that integration of h-2 and intensity of c-2 are affected n ...201526123248
potential of acylated peptides to target the influenza a virus.for antiviral drug design, especially in the field of influenza virus research, potent multivalent inhibitors raise high expectations for combating epidemics and pandemics. among a large variety of covalent and non-covalent scaffold systems for a multivalent display of inhibitors, we created a simple supramolecular platform to enhance the antiviral effect of our recently developed antiviral peptide b (peb(gf)), preventing binding of influenza virus to the host cell. by conjugating the peptide wi ...201526124860
antiviral matrine-type alkaloids from the rhizomes of sophora tonkinensis.three new matrine-type alkaloids, (+)-5α-hydroxyoxysophocarpine (1), (-)-12β-hydroxyoxysophocarpine (2), and (+)-5α-hydroxylemannine (3), along with 14 known analogues, (-)-sophocarpine (4), (-)-5α-hydroxysophocarpine (5), (-)-9α-hydroxysophocarpine (6), (+)-12α-hydroxysophocarpine (7), (-)-12β-hydroxysophocarpine (8), (+)-oxysophocarpine (9), (+)-matrine (10), (+)-sophoranol (11), (+)-9α-hydroxymatrine (12), (-)-14β-hydroxymatrine (13), (+)-oxymatrine (14), (+)-5α-hydroxyoxymatrine (15), (-)-14 ...201526132528
antigenic maps of influenza a(h3n2) produced with human antisera obtained after primary infection.antigenic characterization of influenza viruses is typically based on hemagglutination inhibition (hi) assay data for viral isolates tested against strain-specific postinfection ferret antisera. here, similar virus characterizations were performed using serological data from humans with primary influenza a(h3n2) infection.201626142433
single-dose cpg immunization protects against a heterosubtypic challenge and generates antigen-specific memory t cells.despite extensive research, influenza a virus (iav) remains a major cause of morbidity, mortality, and healthcare expenditure. emerging pandemics from highly pathogenic iav strains, such as h5n1 and pandemic h1n1, highlight the need for universal, cross-protective vaccines. current vaccine formulations generate strain-specific neutralizing antibodies primarily against the outer coat proteins, hemagglutinin and neuraminidase. in contrast to these highly mutable proteins, internal proteins of iav ...201526161083
profile of the porcine acute-phase proteins response following experimental co-infection with h3n2 swine influenza virus and pasteurella multocida.acute phase proteins (apps) are proposed as potential markers of the health status in pigs.201526161700
pregnancy outcome and clinical status of gilts following experimental infection by h1n2, h3n2 and h1n1pdm09 influenza a viruses during the last month of gestation.the present study was planned to study the effect of various subtypes of swine influenza virus (siv) circulating among pigs (h1n2, h3n2 and emerging pandemic strain of h1n1 influenza a virus (h1n1pdm09) on the course of pregnancy in naïve gilts experimentally infected during the last month of pregnancy. in addition, the clinical course of infection, distribution of viruses in various tissues (blood, placenta, fetal lung), and selected immunological, reproductive and productive parameters were al ...201526162303
[genetic diversity and evolution of the m gene of human influenza a viruses from 2009 to 2013 in hangzhou, china].we investigated the genetic diversity and evolution of the m gene of human influenza a viruses in hangzhou (zhejiang province, china) from 2009 to 2013, including subtypes of a(h1n1) pdm09 strains and seasonal a(h3n2) strains. subtypes of analyzed viruses were identified by cell culture and real-time reverse transcription-polymerase chain reaction, followed by cloning, sequencing and phylogenetic analyses of the m gene. assessment of 5675 throat swabs revealed a positive rate for the influenza v ...201526164939
[composites of peptide nucleic acids with titanium dioxide nanoparticles. iv+. antiviral activity of nanocomposites containing dna/pna duplexes].antiviral activity of tio2 · pl · dna/pna nanobiocomposites was studied on the mdck cell culture infected with influenza a virus (subtype h3n2). pna fragment in nanocomposites as a dna/pna heteroduplex is electrostatically bound to titanium dioxide nanoparticles precovered with polylysine (tio2 · pl). it was shown that tio2 · pl · dna1/pna1 nanobiocomposit bearing pna1 fragment targeted to the 3'-end of the noncoding region of segment 5 of viral rna specifically inhibited the virus reproduction ...201526165123
the serine protease inhibitor camostat inhibits influenza virus replication and cytokine production in primary cultures of human tracheal epithelial cells.serine proteases act through the proteolytic cleavage of the hemagglutinin (ha) of influenza viruses for the entry of influenza virus into cells, resulting in infection. however, the inhibitory effects of serine protease inhibitors on influenza virus infection of human airway epithelial cells, and on their production of inflammatory cytokines are unclear.201526166259
hemagglutinin sequence conservation guided stem immunogen design from influenza a h3 subtype.seasonal epidemics caused by influenza a (h1 and h3 subtypes) and b viruses are a major global health threat. the traditional, trivalent influenza vaccines have limited efficacy because of rapid antigenic evolution of the circulating viruses. this antigenic variability mediates viral escape from the host immune responses, necessitating annual vaccine updates. influenza vaccines elicit a protective antibody response, primarily targeting the viral surface glycoprotein hemagglutinin (ha). however, ...201526167164
6sln-lipo pga specifically catches (coats) human influenza virus and synergizes neuraminidase-targeting drugs for human influenza therapeutic potential.the purpose of this study was to develop a new compound to overcome influenza epidemics and pandemics as well as drug resistance.201526169554
gene expression profiles link respiratory viral infection, platelet response to aspirin, and acute myocardial infarction.influenza infection is associated with myocardial infarction (mi), suggesting that respiratory viral infection may induce biologic pathways that contribute to mi. we tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral ges) was associated with mi and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet ges) of platelet function in response to aspirin that is associated with mi.201526193668
phylogeography of influenza a(h3n2) virus in peru, 2010-2012.it remains unclear whether lineages of influenza a(h3n2) virus can persist in the tropics and seed temperate areas. we used viral gene sequence data sampled from peru to test this source-sink model for a latin american country. viruses were obtained during 2010-2012 from influenza surveillance cohorts in cusco, tumbes, puerto maldonado, and lima. specimens positive for influenza a(h3n2) virus were randomly selected and underwent hemagglutinin sequencing and phylogeographic analyses. analysis of ...201526196599
influenza a viruses of human origin in swine, brazil.the evolutionary origins of the influenza a(h1n1)pdm09 virus that caused the first outbreak of the 2009 pandemic in mexico remain unclear, highlighting the lack of swine surveillance in latin american countries. although brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in brazil's swine until the major outbreaks of influenza a(h1n1)pdm09 in 2009. through phylogenetic analysis of whole-genome sequences of influenza viruses of the h1n1, h1n2, an ...201526196759
the global influenza hospital surveillance network (gihsn): a new platform to describe the epidemiology of severe influenza.influenza is a global public health problem. however, severe influenza only recently has been addressed in routine surveillance.201526198771
kolaviron improves morbidity and suppresses mortality by mitigating oxido-inflammation in balb/c mice infected with influenza virus.influenza a viruses (iav) induce cytokine storm and host's intracellular redox imbalance to ensure continuous replication and survival, leading to severe immunopathology and death. the unpredictability of broad-spectrum vaccines, the emergence of drug-resistant and/or more virulent strains, the prevalence of the amantadane-resistant iav, and the prohibitive cost of available drugs especially in resource-poor countries necessitate exploring drugs with novel action mechanisms as anti-influenza age ...201526200137
analysis of influenza transmission in the households of primary and junior high school students during the 2012-13 influenza season in odate, japan.households are one of the major settings of influenza transmission in the community and transmission is frequently initiated by school-aged children. we surveyed households with primary school (ps) and/ or junior high school (jh) children for the 2012-13 influenza season in odate, japan then characterized the epidemiology of influenza household transmission as well as estimated the serial intervals.201526201316
molecular epidemiology and evolution of influenza viruses circulating within european swine between 2009 and 2013.the emergence in humans of the a(h1n1)pdm09 influenza virus, a complex reassortant virus of swine origin, highlighted the importance of worldwide influenza virus surveillance in swine. to date, large-scale surveillance studies have been reported for southern china and north america, but such data have not yet been described for europe. we report the first large-scale genomic characterization of 290 swine influenza viruses collected from 14 european countries between 2009 and 2013. a total of 23 ...201526202246
glycosylation analysis of engineered h3n2 influenza a virus hemagglutinins with sequentially added historically relevant glycosylation sites.the influenza virus surface glycoprotein hemagglutinin (ha) is the major target of host neutralizing antibodies. the oligosaccharides of ha can contribute to ha's antigenic characteristics. after a leap to humans from a zoonotic host, influenza can gain n-glycosylation sequons over time as part of its fitness strategy. this glycosylation expansion has not been studied at the structural level. here we examine ha n-glycosylation of h3n2 virus strains that we have engineered to closely mimic glycos ...201526202417
the virologist and the flu.we report a case of a virologist - who is in age-appropriate medical condition with no relevant chronic diseases - who shed influenza a h3n2 virus rna for 70 days while infectious virus could be detected by cell culture only up to 5 days after onset of symptoms despite a 5-day course of oseltamivir. the case might have implications for infection control in hospital settings and the weighting of the predictive value of pcr results.201526209407
mucosally administered lactobacillus surface-displayed influenza antigens (sm2 and ha2) with cholera toxin subunit a1 (cta1) induce broadly protective immune responses against divergent influenza subtypes.the development of a universal influenza vaccine that provides broad cross protection against existing and unforeseen influenza viruses is a critical challenge. in this study, we constructed and expressed conserved sm2 and ha2 influenza antigens with cholera toxin subunit a1 (cta1) on the surface of lactobacillus casei (pgsa-cta1sm2ha2/l. casei). oral and nasal administrations of recombinant l. casei into mice resulted in high levels of serum immunoglobulin g (igg) and their isotypes (igg1 & igg ...201526210951
antigenic variation of the human influenza a (h3n2) virus during the 2014-2015 winter season.the human influenza a (h3n2) virus dominated the 2014-2015 winter season in many countries and caused massive morbidity and mortality because of its antigenic variation. so far, very little is known about the antigenic patterns of the recent h3n2 virus. by systematically mapping the antigenic relationships of h3n2 strains isolated since 2010, we discovered that two groups with obvious antigenic divergence, named sw13 (a/switzerland/9715293/2013-like strains) and hk14 (a/hong kong/5738/2014-like ...201526219513
prevalence of influenza a/h3n2 virus in northern iran from 2011 to 2013.influenza a virus is the most virulent human pathogen and causes the most serious problem. having epidemiological knowledge about this disease is important. the aim of this study was to determine the prevalence of influenza a/h3n2 virus infection in northern iran from 2011 to 2013 using the real-time polymerase chain reaction (rt-pcr).201526221512
influenza sentinel surveillance among patients with influenza-like-illness and severe acute respiratory illness within the framework of the national reference laboratory, niger, 2009-2013.little is known about the epidemiology of influenza in africa, including niger. we documented the epidemiology of seasonal and pandemic influenza among outpatients with influenza-like-illness (ili) and inpatients with severe acute respiratory illness (sari) presenting at selected sentinel sites in niger from april 2009 through april 2013.201526230666
broadly protective immunity against divergent influenza viruses by oral co-administration of lactococcus lactis expressing nucleoprotein adjuvanted with cholera toxin b subunit in mice.current influenza vaccines need to be annually reformulated to well match the predicated circulating strains. thus, it is critical for developing a novel universal influenza vaccine that would be able to confer cross-protection against constantly emerging divergent influenza virus strains. influenza virus a is a genus of the orthomyxoviridae family of viruses. influenza virus nucleoprotein (np) is a structural protein which encapsidates the negative strand viral rna, and anti-np antibodies play ...201526242406
serum samples from middle-aged adults vaccinated annually with seasonal influenza vaccines cross-neutralize some potential pandemic influenza viruses.we examined serum samples from adults ages 48-64 who received multiple seasonal influenza vaccines from 2004 to 2009 for cross-neutralizing antibodies to potential pandemic strains. using pseudoviruses bearing various hemagglutinins (ha-pseudoviruses), we found serum neutralization titers (≥160) in 100% against a/japan/305/1957 (h2n2), 53% against a/hong kong/1073/99 (h9n2), 56% against the h3n2 variant a/indiana/08/11 (h3n2v), 11% against a/hong kong/g9/97 (h9n2), and 36% a/chicken/hong kong/sf ...201626243315
evolutionary dynamics of influenza a viruses in us exhibition swine.the role of exhibition swine in influenza a virus transmission was recently demonstrated by >300 infections with influenza a(h3n2) variant viruses among individuals who attended agricultural fairs. through active influenza a virus surveillance in us exhibition swine and whole-genome sequencing of 380 isolates, we demonstrate that exhibition swine are actively involved in the evolution of influenza a viruses, including zoonotic strains. first, frequent introduction of influenza a viruses from com ...201626243317
disease risks associated with free-ranging wild boar in saskatchewan.this study investigated the disease status of saskatchewan's feral wild boar population. whole carcasses, tissue samples, and/or serum from 81 hunter-killed boars from saskatchewan were submitted to the canadian wildlife health cooperative (cwhc) between 2009 and 2014. serological tests were negative for prrs, h1n1, and h3n2 swine influenza, pcv-2, and tge/prcv in 22/22 boars and for toxoplasma gondii and mycoplasma hyopneumoniae in 20/20 boars. of 20 boars whose sera were tested 20 were positiv ...026246630
characterization of humoral responses induced by an h7n9 influenza virus-like particle vaccine in balb/c mice.in april 2013, human infections with a novel avian influenza (h7n9) virus emerged in china. it has caused serious concerns for public health throughout the world. however, there is presently no effective treatment, and an a (h7n9) h7 subtype influenza vaccine is not available. vaccination with virus-like particles (vlps) has showed considerable promise for many other subtype influenza viruses. to produce h7n9 vlps, full length, unmodified hemagglutinin (ha), neuraminidase (na), and matrix1 (m1) ...201526248076
co-immunization with tandem repeat heterologous m2 extracellular proteins overcomes strain-specific protection of split vaccine against influenza a virus.current influenza vaccines are less efficacious against antigenically different influenza a viruses. this study presents an approach to overcome strain-specific protection, using a strategy of co-immunization with seasonal h3n2 split vaccine and yeast-expressed soluble proteins of a tandem repeat containing heterologous influenza m2 ectodomains (m2e5x). co-immunization with both vaccines in mice was superior to either vaccine alone in inducing cross protection against heterologous h3n2 virus by ...201526248203
immunogenicity and sustainability of the immune response in brazilian hiv-1-infected individuals vaccinated with inactivated triple influenza vaccine.hiv-infected individuals have a higher risk of serious illnesses following infection by infection with influenza. although anti-influenza vaccination is recommended, immunosuppression may limit their response to active immunization. we followed-up a cohort of hiv-infected individuals vaccinated against influenza to assess the immunogenicity and sustainability of the immune response to vaccination. individuals were vaccinated 2011 with inactivated triple influenza vaccine (tiv), and they had rece ...201626267817
immunogenicity and safety of an inactivated quadrivalent influenza vaccine in healthy adults: a phase ii, open-label, uncontrolled trial in japan.two antigenically distinct b strain lineages of influenza virus have co-circulated since the mid-1980s; however, inactivated trivalent influenza vaccines contain only one b lineage. the mismatch between the circulating and vaccine lineages has been a worldwide issue. in this study, an inactivated quadrivalent influenza vaccine (qiv) candidate containing two b lineages was manufactured and its immunogenicity and safety evaluated in an open-label, uncontrolled trial. in this phase ii trial, 50 sub ...201526272602
establishment of functional influenza virus-specific cd8(+) t cell memory pools after intramuscular immunization.the emergence of the avian-origin influenza h7n9 virus and its pandemic potential has highlighted the ever-present need to develop vaccination approaches to induce cross-protective immunity. in this study, we examined the establishment of cross-reactive cd8(+) t cell immunity in mice following immunization with live a/puerto rico/8/1934 (pr8; h1n1) influenza virus via two non-productive inoculation routes. we found that immunization via the intramuscular (im) route established functional influen ...201526277069
a broadly neutralizing human monoclonal antibody is effective against h7n9.emerging strains of influenza represent a significant public health threat with potential pandemic consequences. of particular concern are the recently emerged h7n9 strains which cause pneumonia with acute respiratory distress syndrome. estimates are that nearly 80% of hospitalized patients with h7n9 have received intensive care unit support. vis410, a human antibody, targets a unique conserved epitope on influenza a. we evaluated the efficacy of vis410 for neutralization of group 2 influenza st ...201526283346
detection of influenza a(h3n2) virus in children with suspected mumps during winter 2014/15 in england.influenza a(h3n2) virus was detected in oral fluid from 16/107 children (aged 2 to 12 years) with a clinical diagnosis of mumps, who were sampled between december 2014 and february 2015 in england, during the peak of the 2014/15 influenza season. sequence analysis of an a(h3n2) virus from a child with suspected mumps showed the virus was similar to other circulating a(h3n2) viruses detected in winter 2014/15, which were antigenically drifted from the a(h3n2) vaccine strain.201526290428
age-related prevalence of cross-reactive antibodies against influenza a(h3n2) variant virus, germany, 2003 to 2010.to estimate susceptibility to the swine-origin influenza a(h3n2) variant virus (a(h3n2)v) in the german population, we investigated cross-reactive antibodies against this virus and factors associated with seroprotective titre using sera from representative health examination surveys of children and adolescents (n = 815, 2003–06) and adults (n = 600, 2008–10). antibodies were assessed by haemagglutination inhibition assay (hi); in our study an hi titre ≥ 40 was defined as seroprotective. we inves ...201526290488
sialic acid-dependent interactions between influenza viruses and streptococcus suis affect the infection of porcine tracheal cells.bacterial co-infections are a major complication in influenza-virus-induced disease in both humans and animals. either of the pathogens may induce a host response that affects the infection by the other pathogen. a unique feature in the co-infection by swine influenza viruses (siv) and streptococcus suis serotype 2 is the direct interaction between the two pathogens. it is mediated by the haemagglutinin of siv that recognizes the α2,6-linked sialic acid present in the capsular polysaccharide of ...201526297001
incidence of medically attended influenza during pandemic and post-pandemic seasons through the influenza incidence surveillance project, 2009-13.since the introduction of pandemic influenza a (h1n1) to the usa in 2009, the influenza incidence surveillance project has monitored the burden of influenza in the outpatient setting through population-based surveillance.201526300111
[susceptibility of human influenza a (h3n2) viruses to neuraminidase inhibitors isolated during 2011-2012 in china].to analyze the susceptibility of influenza a (h3n2) viruses to neuraminidase inhibitors during 2011-2012 in mainland china.201526310330
cross-species infectivity of h3n8 influenza virus in an experimental infection in swine.avian influenza a viruses have gained increasing attention due to their ability to cross the species barrier and cause severe disease in humans and other mammal species as pigs. h3 and particularly h3n8 viruses, are highly adaptive since they are found in multiple avian and mammal hosts. h3n8 viruses have not been isolated yet from humans; however, a recent report showed that equine influenza a viruses (iavs) can be isolated from pigs, although an established infection has not been observed thus ...201526311894
novel reassortant human-like h3n2 and h3n1 influenza a viruses detected in pigs are virulent and antigenically distinct from swine viruses endemic to the united states.human-like swine h3 influenza a viruses (iav) were detected by the usda surveillance system. we characterized two novel swine human-like h3n2 and h3n1 viruses with hemagglutinin (ha) genes similar to those in human seasonal h3 strains and internal genes closely related to those of 2009 h1n1 pandemic viruses. the h3n2 neuraminidase (na) was of the contemporary human n2 lineage, while the h3n1 na was of the classical swine n1 lineage. both viruses were antigenically distant from swine h3 viruses t ...201526311895
sex differences in h7n9 influenza a virus pathogenesis.sex, gender and age have an impact on incidence and severity of several infectious diseases. here, we analyzed reported human cases of avian h7n9 influenza a virus infections for potential sex-dependent incidence and mortality. we report that females in their reproductive years display an increased tendency to die of h7n9 influenza than males (female-to-male ratio=1.2). next, we challenged this potential sex-dependent difference in influenza disease outcome using a mouse infection model. in gene ...201526319064
antiviral activity of an aqueous extract derived from aloe arborescens mill. against a broad panel of viruses causing infections of the upper respiratory tract.a number of antiviral therapies have evolved that may be effectively administered to treat respiratory viral diseases. but these therapies are very often of limited efficacy or have severe side effects. therefore there is great interest in developing new efficacious and safe antiviral compounds e.g. based on the identification of compounds of herbal origin.201526321740
clinical characteristics are similar across type a and b influenza virus infections.studies that aimed at comparing the clinical presentation of influenza patients across virus types and subtypes/lineages found divergent results, but this was never investigated using data collected over several years in a countrywide, primary care practitioners-based influenza surveillance system.201526325069
reconstruction of the evolutionary dynamics of a(h3n2) influenza viruses circulating in italy from 2004 to 2012.influenza a viruses are characterised by their rapid evolution, and the appearance of point mutations in the viral hemagglutinin (ha) domain causes seasonal epidemics. the a(h3n2) virus has higher mutation rate than the a(h1n1) virus. the aim of this study was to reconstruct the evolutionary dynamics of the a(h3n2) viruses circulating in italy between 2004 and 2012 in the light of the forces driving viral evolution.201526331945
development of high-yield influenza a virus vaccine viruses.vaccination is one of the most cost-effective ways to prevent infection. influenza vaccines propagated in cultured cells are approved for use in humans, but their yields are often suboptimal. here, we screened a/puerto rico/8/34 (pr8) virus mutant libraries to develop vaccine backbones (defined here as the six viral rna segments not encoding haemagglutinin and neuraminidase) that support high yield in cell culture. we also tested mutations in the coding and regulatory regions of the virus, and c ...201526334134
viral dominance of reassortants between canine influenza h3n2 and pandemic (2009) h1n1 viruses from a naturally co-infected dog.since avian-origin h3n2 canine influenza virus (civ) was first identified in south korea in 2008, the novel influenza virus has been reported in several countries in asia. reverse zoonotic transmission of pandemic h1n1 (2009) influenza virus (ph1n1) has been observed in a broad range of animal species. viral dominance and characterization of the reassortants of both viruses was undertaken in the present study.201526336880
influenza a virus infection in brazilian swine herds following the introduction of pandemic 2009 h1n1.influenza a virus (fluav) infections are endemic in pork producing countries worldwide but in brazil it was not considered an important pathogen in pigs. since the emergence of 2009 pandemic h1n1 (h1n1pdm) fluav, many outbreaks of respiratory disease were observed in pig herds. the aim of this study was to evaluate fluav infection in swine in 48 pig farms located in seven brazilian states with previous reports of influenza-like signs by clinical, serological and virological cross-sectional studi ...201526345257
influenza virus surveillance in argentina during the 2012 season: antigenic characterization, genetic analysis and antiviral susceptibility.the activity and circulation of influenza viruses in argentina was studied during 2012 as part of the argentinean surveillance for influenza and other respiratory viruses, in the context of global influenza surveillance. the antigenicity and molecular characteristics of haemagglutinins (ha) of circulating influenza a and b viruses were analysed to assess the emergence of virus variants. susceptibility to oseltamivir and zanamivir was evaluated by enzymatic assay and results were backed-up by seq ...201626345289
novel human-like influenza a viruses circulate in swine in mexico and chile.further understanding of the genetic diversity and evolution of influenza a viruses circulating in swine (iav-s) is important for the development of effective vaccines and our knowledge of pandemic threats. until recently, very little was known of iav-s diversity in latin america, owing to a lack of surveillance.201526345598
in silico identification of highly conserved epitopes of influenza a h1n1, h2n2, h3n2, and h5n1 with diagnostic and vaccination potential.the unpredictable, evolutionary nature of the influenza a virus (iav) is the primary problem when generating a vaccine and when designing diagnostic strategies; thus, it is necessary to determine the constant regions in viral proteins. in this study, we completed an in silico analysis of the reported epitopes of the 4 iav proteins that are antigenically most significant (ha, na, np, and m2) in the 3 strains with the greatest world circulation in the last century (h1n1, h2n2, and h3n2) and in one ...201526346523
recommendations for prevention and control of influenza in children, 2015-2016.the purpose of this statement is to update recommendations for routine use of seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. the american academy of pediatrics recommends annual seasonal influenza immunization for all people 6 months and older, including all children and adolescents. highlights for the upcoming 2015-2016 season include the following: 1. annual universal influenza immunization is indicated with either a trivalent or ...201526347430
[analysis of the mechanism of a three-wave epidemic influenza a virus cvcle].a three-wave epidemic cycle caused by a new serotype agent is simulated. the mechanism of stepwise recession in a stratum of the susceptible persons is examined. a group of asymptomatic infected individuals as well as an antigen activity index, which regulates the intensity of input streams into the groups of infected patients, are introduced into the model. morbidity rate is additionally regulated by the virulence. the model is identified according to the observations of the three-wave passage ...201526349219
in vitro validation of self designed "universal human influenza a sirna".the genomic variability of influenza a virus (iav) makes it difficult for the existing vaccines or anti-influenza drugs to control. the sirna targeting viral gene induces rnai mechanism in the host and silent the gene by cleaving mrna. in this study, we developed an universal sirna and validated its efficiency in vitro. the sirna was designed rationally, targeting the most conserved region (delineated with the help of multiple sequence alignment) of m gene of iav strains. three level screening m ...201526349314
evaluation of commercial diagnostic assays for the specific detection of avian influenza a (h7n9) virus rna using a quality-control panel and clinical specimens in china.a novel avian influenza a h7n9-subtype virus emerged in china in 2013 and threatened global public health. commercial kits that specifically detect avian influenza a (h7n9) virus rna are urgently required to prepare for the emergence and potential pandemic of this novel influenza virus. the safety and effectiveness of three commercial molecular diagnostic assays were evaluated using a quality-control panel and clinical specimens collected from over 90 patients with confirmed avian influenza a (h ...201526361351
cross protection against influenza a virus by yeast-expressed heterologous tandem repeat m2 extracellular proteins.the influenza m2 ectodomain (m2e) is well conserved across human influenza a subtypes, but there are few residue changes among avian and swine origin influenza a viruses. we expressed a tandem repeat construct of heterologous m2e sequences (m2e5x) derived from human, swine, and avian origin influenza a viruses using the yeast expression system. intramuscular immunization of mice with as04-adjuvanted m2e5x protein vaccines was effective in inducing m2e-specific antibodies reactive to m2e peptide ...201526366729
insight flu005: an anti-influenza virus hyperimmune intravenous immunoglobulin pilot study.hemagglutination inhibition (hai) antibody responses to anti-influenza virus hyperimmune intravenous immunoglobulin (hivig) were characterized. thirty-one patients with influenza during the 2013-2014 season were randomly assigned to receive 0.25 g/kg of hivig (n = 16) or placebo (n = 15). for hivig recipients, the ratio of geometric mean titers (1 hour after infusion/before infusion) was 4.00 (95% confidence interval [ci], 2.61-6.13) for 2009 pandemic influenza a(h1n1) and 1.76 (95% ci, 1.33-2.3 ...201626374911
rig-i signaling is essential for influenza b virus-induced rapid interferon gene expression.influenza b virus causes annual epidemics and, along with influenza a virus, accounts for substantial disease and economic burden throughout the world. influenza b virus infects only humans and some marine mammals and is not responsible for pandemics, possibly due to a very low frequency of reassortment and a lower evolutionary rate than that of influenza a virus. influenza b virus has been less studied than influenza a virus, and thus, a comparison of influenza a and b virus infection mechanism ...201526378160
role of substitutions in the hemagglutinin in the emergence of the 1968 pandemic influenza virus.hemagglutinin (ha) of h3n2/1968 pandemic influenza viruses differs from the putative avian precursor by seven amino acid substitutions. substitutions q226l and g228s are known to be essential for adaptation of avian ha to mammals. we found that introduction of avian-virus-like amino acids at five other ha positions (positions 62, 81, 92, 144, and 193) of a/hong kong/1/1968 virus decreased viral replication in human cells and transmission in pigs. thus, substitutions at some of these positions fa ...201526378170
attenuated recombinant influenza a virus expressing hpv16 e6 and e7 as a novel therapeutic vaccine approach.persistent infection with high-risk human papillomavirus (hpv) types, most often hpv16 and hpv18, causes all cervical and most anal cancers, and a subset of vulvar, vaginal, penile and oropharyngeal carcinomas. two prophylactic virus-like particle (vlps)-based vaccines, are available that protect against vaccine type-associated persistent infection and associated disease, yet have no therapeutic effect on existing lesions or infections. we have generated recombinant live-attenuated influenza a v ...201526381401
sexual diergism in antibody response to whole virus trivalent inactivated influenza vaccine in outbred mice.an outbred mouse model was used to determine if antibody response to immunization with whole-virus trivalent inactivated influenza vaccine (tiv) differs between the sexes. the antibody response was examined one (serum titer of igm antibodies), and three and six weeks post-immunization (serum titer of neutralizing and total igg antibodies and igg subclass profile). compared with male in female mice was found (i) the more robust igm response against all influenza strains included in tiv and (ii) m ...201526382601
diagnostic potential of recombinant scfv antibodies generated against hemagglutinin protein of influenza a virus.human influenza a viruses have been the cause of enormous socio-economic losses worldwide. in order to combat such a notorious pathogen, hemagglutinin protein (ha) has been a preferred target for generation of neutralizing-antibodies as potent therapeutic/diagnostic agents. in the present study, recombinant anti-ha single chain variable fragment antibodies were constructed using the phage-display technology to aid in diagnosis and treatment of human influenza a virus infections. spleen cells of ...201526388868
update: influenza activity--united states and worldwide, may 24-september 5, 2015.during may 24–september 5, 2015, the united states experienced typical low levels of seasonal influenza activity. influenza a (h1n1)pdm09 (ph1n1), influenza a (h3n2), and influenza b viruses were detected worldwide and were identified sporadically in the united states. all of the influenza viruses collected from u.s. states and other countries during that time have been characterized antigenically and/or genetically as being similar to the influenza vaccine viruses recommended for inclusion in t ...201526390411
new functionally-enhanced soy proteins as food ingredients with anti-viral activity.respiratory viruses are a major public health problem because of their prevalence and high morbidity rate leading to considerable social and economic implications. cranberry has therapeutic potential attributed to a comprehensive list of phytochemicals including anthocyanins, flavonols, and unique a-type proanthocyanidins. soy flavonoids, including isoflavones, have demonstrated anti-viral effects in vitro and in vivo. recently, it was demonstrated that edible proteins can efficiently sorb and c ...201526396978
identification of conserved peptides comprising multiple t cell epitopes of matrix 1 protein in h1n1 influenza virus.cell mediated immune response plays a key role in combating viral infection and thus identification of new vaccine targets manifesting t cell mediated response may serve as an ideal approach for influenza vaccine. the present study involves the application of an immunoinformatics-based consensus approach for epitope prediction (three epitope prediction tools each for cd4+ and cd8+ t cell epitopes) and molecular docking to identify peptide sequences containing t cell epitopes using the conserved ...201526398199
influenza virus surveillance in coordinated swine production systems, united states.to clarify the epidemiology of influenza a viruses in coordinated swine production systems to which no animals from outside the system are introduced, we conducted virologic surveillance during september 2012-september 2013. animal age, geographic location, and farm type were found to affect the prevalence of these viruses.201526402228
cross-protection against european swine influenza viruses in the context of infection immunity against the 2009 pandemic h1n1 virus: studies in the pig model of influenza.pigs are natural hosts for the same influenza virus subtypes as humans and are a valuable model for cross-protection studies with influenza. in this study, we have used the pig model to examine the extent of virological protection between a) the 2009 pandemic h1n1 (ph1n1) virus and three different european h1 swine influenza virus (siv) lineages, and b) these h1 viruses and a european h3n2 siv. pigs were inoculated intranasally with representative strains of each virus lineage with 6- and 17-wee ...201526404790
clinical outcome of laninamivir octanoate hydrate for influenza in the 2013-2014 japanese season.the clinical outcome of laninamivir octanoate hydrate (laninamivir) in the japanese 2013-2014 influenza season was investigated. a total of 235 patients were enrolled, of whom 222 were evaluated for the duration of fever and other symptoms. the types/subtypes were 101 a(h1n1)pdm09 (45.5%), 37 a(h3n2) (16.7%), and 84 b (37.8%). the median durations of fever were 32.0, 41.0, and 50.0 h, and the median durations of symptoms were 74.5, 85.0, and 95.0 h for a(h1n1)pdm09, a(h3n2), and b, respectively. ...201526410550
influenza virus survival in aerosols and estimates of viable virus loss resulting from aerosolization and air-sampling.using a collison nebulizer, aerosols of influenza (a/udorn/307/72 h3n2) were generated within a controlled experimental chamber, from known starting virus concentrations. air samples collected after variable suspension times were tested quantitatively using both plaque and polymerase chain reaction assays, to compare the proportion of viable virus against the amount of detectable viral rna. these experiments showed that whereas influenza rna copies were well preserved, the number of viable virus ...201526412395
diversity in compartmental dynamics of gene regulatory networks: the immune response in primary influenza a infection in mice.current approaches to study transcriptional profiles post influenza infection typically rely on tissue sampling from one or two sites at a few time points, such as spleen and lung in murine models. in this study, we infected female c57/bl6 mice intranasally with mouse-adapted h3n2/hong kong/x31 avian influenza a virus, and then analyzed the gene expression profiles in four different compartments (blood, lung, mediastinal lymph nodes, and spleen) over 11 consecutive days post infection. these dat ...201526413862
interim estimates of divergence date and vaccine strain match of human influenza a(h3n2) virus from systematic influenza surveillance (2010-2015) in hangzhou, southeast of china.in the post-pandemic period 2010-2015, seasonal influenza a(h3n2) virus predominated in hangzhou, southeast of china, with an increased activity and semi-annual seasons. this study utilized ha virus gene segment sequences to analyze the divergence date and vaccine strain match of human influenza a(h3n2) virus from systematic influenza surveillance in hangzhou.201526417878
quantifying protection against influenza virus infection measured by hemagglutination-inhibition assays in vaccine trials.correlations between hemagglutination-inhibition titers (hereafter "titers") and protection against infection have been identified in historical studies. however, limited information is available about the dynamics of how titer influences protection.201626427723
detection and isolation of swine influenza a virus in spiked oral fluid and samples from individually housed, experimentally infected pigs: potential role of porcine oral fluid in active influenza a virus surveillance in swine.the lack of seasonality of swine influenza a virus (swiav) in combination with the capacity of swine to harbor a large number of co-circulating iav lineages, resulting in the risk for the emergence of influenza viruses with pandemic potential, stress the importance of swiav surveillance. to date, active surveillance of swiav worldwide is barely done because of the short detection period in nasal swab samples. therefore, more sensitive diagnostic methods to monitor circulating virus strains are r ...201526431039
addition of n-glycosylation sites on the globular head of the h5 hemagglutinin induces the escape of highly pathogenic avian influenza a h5n1 viruses from vaccine-induced immunity.highly pathogenic avian influenza a h5n1 viruses remain endemic in poultry in several countries and still constitute a pandemic threat. since the early 20th century, we experienced four influenza a pandemics. h3n2 and h1n1pdm09 viruses that respectively emerged during 1968 and 2009 pandemics are still responsible for seasonal epidemics. these viruses evolve regularly by substitutions in antigenic sites of the hemagglutinin (ha), which prevent neutralization by antibodies directed against previou ...201526433051
epidemiology of influenza viruses from 2009 to 2013 - a sentinel surveillance report from union territory of puducherry, india.to report the findings of influenza surveillance programme from union territory of puducherry and to document the clinical and epidemiological data of influenza viruses over a five year period from 2009 to 2013.201526433657
assessing antigenic drift of seasonal influenza a(h3n2) and a(h1n1)pdm09 viruses.under selective pressure from the host immune system, antigenic epitopes of influenza virus hemagglutinin (ha) have continually evolved to escape antibody recognition, termed antigenic drift. we analyzed the genomes of influenza a(h3n2) and a(h1n1)pdm09 virus strains circulating in thailand between 2010 and 2014 and assessed how well the yearly vaccine strains recommended for the southern hemisphere matched them. we amplified and sequenced the ha gene of 120 a(h3n2) and 81 a(h1n1)pdm09 influenza ...201526440103
influenza virus reassortment is enhanced by semi-infectious particles but can be suppressed by defective interfering particles.a high particle to infectivity ratio is a feature common to many rna viruses, with ~90-99% of particles unable to initiate a productive infection under low multiplicity conditions. a recent publication by brooke et al. revealed that, for influenza a virus (iav), a proportion of these seemingly non-infectious particles are in fact semi-infectious. semi-infectious (si) particles deliver an incomplete set of viral genes to the cell, and therefore cannot support a full cycle of replication unless co ...201526440404
development of single-chain variable fragments (scfv) against influenza virus targeting hemagglutinin subunit 2 (ha2).influenza a viruses (iav) are widespread in birds and domestic poultry, occasionally causing severe epidemics in humans and posing health threats. hence, the need to develop a strategy for prophylaxis or therapy, such as a broadly neutralizing antibody against iav, is urgent. in this study, single-chain variable fragment (scfv) phage display technology was used to select scfv fragments recognizing influenza envelope proteins. the tomlinson i and j scfv phage display libraries were screened again ...201626446888
lipid composition of viral envelope of three strains of influenza virus - not all viruses are created equal.while differences in the rate of virus fusion and budding from the host cell membrane have been correlated with pathogenicity, no systematic study of the contribution of differences in viral envelope composition has previously been attempted. using rigorous virus purification, marked differences between virions and host were observed. over 125 phospholipid species have been quantitated for three strains of influenza (hkx31- h3n2, pr8- h1n1, and vn1203- h5n1) grown in eggs. the glycerophospholipi ...201526448476
the coexistence or replacement of two subtypes of influenza.a pandemic subtype of influenza a sometimes replaces but sometimes coexists with the previous seasonal subtype. for example, the 1957 pandemic subtype h2n2 replaced the seasonal subtype h1n1; whereas after 1977 subtypes h1n1 (from the pandemic) and h3n2 continue to coexist. in an attempt to understand these alternatives, a hybrid model for the dynamics of influenza a is formulated. during an epidemic season the model takes into account cross-immunity of strains depending on the most recent seaso ...201526453807
oseltamivir population pharmacokinetics in the ferret: model application for pharmacokinetic/pharmacodynamic study design.the ferret is a suitable small animal model for preclinical evaluation of efficacy of antiviral drugs against various influenza strains, including highly pathogenic h5n1 viruses. rigorous pharmacokinetics/pharmacodynamics (pk/pd) assessment of ferret data has not been conducted, perhaps due to insufficient information on oseltamivir pk. here, based on pk data from several studies on both uninfected and influenza-infected groups (i.e., with influenza a viruses of h5n1 and h3n2 subtypes and an inf ...201526460484
aureonitol, a fungi-derived tetrahydrofuran, inhibits influenza replication by targeting its surface glycoprotein hemagglutinin.the influenza virus causes acute respiratory infections, leading to high morbidity and mortality in groups of patients at higher risk. antiviral drugs represent the first line of defense against influenza, both for seasonal infections and pandemic outbreaks. two main classes of drugs against influenza are in clinical use: m2-channel blockers and neuraminidase inhibitors. nevertheless, because influenza strains that are resistant to these antivirals have been described, the search for novel compo ...201526462111
pb1-f2 protein does not impact the virulence of triple-reassortant h3n2 swine influenza virus in pigs but alters pathogenicity and transmission in turkeys.pb1-f2 protein, the 11th influenza a virus (iav) protein, is considered to play an important role in primary influenza virus infection and postinfluenza secondary bacterial pneumonia in mice. the functional role of pb1-f2 has been reported to be a strain-specific and host-specific phenomenon. its precise contribution to the pathogenicity and transmission of influenza virus in mammalian host, such as swine, and avian hosts, such as turkeys, remain largely unknown. in this study, we explored the r ...201526468540
h3n2 mismatch of 2014-15 northern hemisphere influenza vaccines and head-to-head comparison between human and ferret antisera derived antigenic maps.the poor performance of 2014-15 northern hemisphere (nh) influenza vaccines was attributed to mismatched h3n2 component with circulating epidemic strains. using human serum samples collected from 2009-10, 2010-11 and 2014-15 nh influenza vaccine trials, we assessed their cross-reactive hemagglutination inhibition (hai) antibody responses against recent h3 epidemic isolates. all three populations (children, adults, and older adults) vaccinated with the 2014-15 nh egg- or cell-based vaccine, showe ...201526472175
serological evidence of pandemic h1n1 influenza virus infections in greek swine.the introduction of the 2009 pandemic h1n1 (ph1n1) influenza virus in pigs changed the epidemiology of influenza a viruses (iavs) in swine in europe and the rest of the world. previously, three iav subtypes were found in the european pig population: an avian-like h1n1 and two reassortant h1n2 and h3n2 viruses with human-origin haemagglutinin (ha) and neuraminidase proteins and internal genes of avian decent. these viruses pose antigenically distinct has, which allow the retrospective diagnosis o ...201626477456
identification of the ifn-β response in h3n2 canine influenza virus infection.canine influenza viruses (civs) circulate continuously in the dog population, providing opportunities for exposure to humans and other species. although the dog genome has been sequenced, innate immunity in dogs is not well characterized, which limits the understanding of h3n2 canine influenza virus pathogenesis. equally, how this virus evades the canine host innate immune response to successfully establish infection remains unclear. to analyse the ifn-β response to civ infection in madin-darby ...201626490006
identification of a novel viral protein expressed from the pb2 segment of influenza a virus.over the past 2 decades, several novel influenza virus proteins have been identified that modulate viral infections in vitro and/or in vivo. the pb2 segment, which is one of the longest influenza a virus segments, is known to encode only one viral protein, pb2. in the present study, we used reverse transcription-pcr (rt-pcr) targeting viral mrnas transcribed from the pb2 segment to look for novel viral proteins encoded by spliced mrnas. we identified a new viral protein, pb2-s1, encoded by a nov ...201526491155
ceftiofur hydrochloride affects the humoral and cellular immune response in pigs after vaccination against swine influenza and pseudorabies.cephalosporins are a class of antibiotics that are active against many gram-positive and some gram-negative bacteria. beyond their antibacterial activity, they are reported to have various immunomodulatory properties. it has been shown that they reduce the secretion of cytokines as well as influence the humoral and cellular immune response. in the field conditions antibiotics are frequently administered at the same time as vaccines in pigs and, in the view of their potential immunomodulatory pro ...201526493336
[child and adolescent interepydemic immunity to influenza viruses].our aim was to evaluate the child and adolescent population immunity to influenza a viruses (iav) and influenza b virus (ibv).201526495719
icam-1 regulates the survival of influenza virus in lung epithelial cells during the early stages of infection.intercellular cell adhesion molecule-1 (icam-1) is an inducible cell surface glycoprotein that is expressed on many cell types. influenza virus infection enhanced icam-1 expression and messenger rna levels. human bronchial epithelial cells (hbepc) and nasal epithelial cells, on exposure to different strains of influenza virus (h1n1, h3n2, and h9n1) showed significant increase in icam-1 gene expression (p<0.001) along with the icam-1 protein levels (surface and secreted). depleting icam-1 in hbep ...201626499045
differential evolution of peripheral cytokine levels in symptomatic and asymptomatic responses to experimental influenza virus challenge.exposure to influenza virus triggers a complex cascade of events in the human host. in order to understand more clearly the evolution of this intricate response over time, human volunteers were inoculated with influenza a/wisconsin/67/2005 (h3n2), and then had serial peripheral blood samples drawn and tested for the presence of 25 major human cytokines. nine of 17 (53%) inoculated subjects developed symptomatic influenza infection. individuals who will go on to become symptomatic demonstrate inc ...201626506932
human micrornas profiling in response to influenza a viruses (subtypes ph1n1, h3n2, and h5n1).micrornas (mirnas) play an important role in regulation of gene silencing and are involved in many cellular processes including inhibition of infected viral replication. this study investigated cellular mirna expression profiles operating in response to influenza virus in early stage of infection which might be useful for understanding and control of viral infection. a549 cells were infected with different subtypes of influenza virus (ph1n1, h3n2 and h5n1). after 24 h post-infection, mirnas were ...201626518627
impact of a large deletion in the neuraminidase protein identified in a laninamivir-selected influenza a/brisbane/10/2007 (h3n2) variant on viral fitness in vitro and in ferrets.viral fitness of a laninamivir-selected influenza a/brisbane/10/2007-like (h3n2) isolate (lrvp9) containing a 237-amino acid neuraminidase deletion and a p194l hemagglutinin mutation was evaluated in vitro and in ferrets. lrvp9 and the wild-type (wt) virus showed comparable replication kinetics in mdck-st6gali cells. cultured virus was recovered between days 2 and 5 post-infection in nasal washes (nw) from the 4 wt-infected ferrets whereas no virus was recovered from the lrvp9-infected animals. ...201626526406
detection of influenza a(h3n2) clade 3c.2a viruses in patients with suspected mumps in british columbia, canada, during the 2014/15 influenza season. 201526536131
antiviral activities of several oral traditional chinese medicines against influenza viruses.influenza is still a serious threat to human health with significant morbidity and mortality. the emergence of drug-resistant influenza viruses poses a great challenge to existing antiviral drugs. traditional chinese medicines (tcms) may be an alternative to overcome the challenge. here, 10 oral proprietary chinese medicines were selected to evaluate their anti-influenza activities. these drugs exhibit potent inhibitory effects against influenza a h1n1, influenza a h3n2, and influenza b virus. i ...201526557857
topical imiquimod before intradermal trivalent influenza vaccine for protection against heterologous non-vaccine and antigenically drifted viruses: a single-centre, double-blind, randomised, controlled phase 2b/3 trial.pretreatment with topical imiquimod, a synthetic agonist of toll-like receptor 7, significantly improved the immunogenicity of influenza vaccination in elderly people. we aimed to clarify its effect in a younger age group.201626559482
influenza surveillance in russia based on epidemiological and laboratory data for the period from 2005 to 2012.exchange of information on and sharing of influenza viruses through the gisrs network has great significance for understanding influenza virus evolution, recognition of a new pandemic virus emergence and for preparing annual who recommendations on influenza vaccine strain composition. influenza surveillance in russia is based on collaboration of two nics with 59 regional bases. most epidemiological and laboratory data are entered through the internet into the electronic database at the research ...201726561480
the clinical usefulness of lymphocyte:monocyte ratios in differentiating influenza from viral non-influenza-like illnesses in hospitalized adults during the 2015 influenza a (h3n2) epidemic: the uniqueness of hpiv-3 mimicking influenza a.during influenza epidemics, influenza-like illnesses (ilis) viruses cocirculate with influenza strains. if positive, rapid influenza diagnostic tests (ridts) identify influenza a/b, but false-negative ridts require retesting by viral polymerase chain reaction (pcr). patient volume limits testing during influenza epidemics, and non-specific laboratory findings have been used for presumptive diagnosis pending definitive viral testing. in adults, the most useful laboratory abnormalities in influenz ...201626563893
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