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international laboratory comparison of influenza microneutralization assays for a(h1n1)pdm09, a(h3n2), and a(h5n1) influenza viruses by consise.the microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. these protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. the impact these protocol variations have on influenza serology data is unclear. thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (elisa) and 3-day h ...201526108286
virus-neutralizing antibody response of mice to consecutive infection with human and avian influenza a viruses.in this work we simulated in a mouse model a naturally occurring situation of humans, who overcame an infection with epidemic strains of influenza a, and were subsequently exposed to avian influenza a viruses (iav). the antibody response to avian iav in mice previously infected with human iav was analyzed. we used two avian iav (a/duck/czechoslovakia/1956 (h4n6) and the attenuated virus ra/viet nam/1203-2004 (h5n1)) as well as two human iav isolates (virus a/mississippi/1/1985 (h3n2) of medium v ...201526104333
in vitro neuraminidase inhibitory activity of four neuraminidase inhibitors against clinical isolates of the influenza virus circulating in the japanese 2013-2014 season.to assess the extent of viral resistance, we measured the 50% inhibitory concentration (ic50) of neuraminidase inhibitors (nais) for the influenza virus isolates in the 2013-2014 influenza season and compared the results to those of the 2010-2011 to 2012-2013 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 neuraminidase inhi ...201526096495
influenza virus activating host proteases: identification, localization and inhibitors as potential therapeutics.cellular proteases are reponsible for activation of influenza virus hemagglutinin (ha) in epithelial tissues of the respiratory tract. the trans-golgi network (tgn) is the main subcellular compartment where ha cleavage occurs during its biosynthesis. the proteolytic ha cleavage is an indispensable prerequisite for the fusion of viral with endosomal membrane and the delivery of the virus genome into the cell. both, the structure and accessibility of the ha cleavage site determine the responsible ...201526095298
paper-based enzyme-free immunoassay for rapid detection and subtyping of influenza a h1n1 and h3n2 viruses.development of rapid screening in the ambulatory environment is the most pressing needs for the control of spread of infectious disease. despite there are many methods to detect the immunoassay results, quantitative measurement in rapid disease screening is still a great challenge for point-of-care applications. in this work, based on the internal structural protein, i.e., nucleoprotein (np), and outer surface glycoproteins, i.e., h1 and h3, of the influenza viruses, specific and sensitive immun ...201526088774
the role of human transportation networks in mediating the genetic structure of seasonal influenza in the united states.recent studies have demonstrated the importance of accounting for human mobility networks when modeling epidemics in order to accurately predict spatial dynamics. however, little is known about the impact these movement networks have on the genetic structure of pathogen populations and whether these effects are scale-dependent. we investigated how human movement along the aviation and commuter networks contributed to intra-seasonal genetic structure of influenza a epidemics in the continental un ...201526086273
immunological persistence of a seasonal influenza vaccine in people more than 3 years old.to evaluate antibody persistence of aleph inactivated split influenza vaccine, 3308 healthy chinese people more than 3 years old were enrolled in a hemagglutination inhibition (hi) assay before vaccination, 641 were screened by hi assay negative, 437 of which received one dose of aleph inactivated split influenza vaccine and 204 of which received one dose of control vaccine (recombinant hepatitis b). after vaccination, the receivers were collected blood at 1st month, 3rd month, 6th month and 12t ...201526083828
boosted influenza-specific t cell responses after h5n1 pandemic live attenuated influenza virus vaccination.in a phase i clinical trial, a h5n1 pandemic live attenuated influenza virus (plaiv) vn2004 vaccine bearing avian influenza h5n1 hemagglutinin (ha) and na genes on the a/ann arbor cold-adapted vaccine backbone displayed very restricted replication. we evaluated t cell responses to h5n1 plaiv vaccination and assessed pre-existing t cell responses to determine whether they were associated with restricted replication of the h5n1 plaiv.201526082783
determination of predominance of influenza virus strains in the americas.during 2001-2014, predominant influenza a(h1n1) and a(h3n2) strains in south america predominated in all or most subsequent influenza seasons in central and north america. predominant a(h1n1) and a(h3n2) strains in north america predominated in most subsequent seasons in central and south america. sharing data between these subregions may improve influenza season preparedness.201526079140
optimization of a micro-neutralisation assay and its application in antigenic characterisation of influenza viruses.the identification of antigenic variants and the selection of influenza viruses for vaccine production are based largely on antigenic characterisation of the haemagglutinin (ha) of circulating viruses using the haemagglutination inhibition (hi) assay. however, additional to evolution related to escape from host immunity, variants emerging as a result of propagation in different cell substrates can complicate interpretation of hi results.201526073976
viral subpopulation diversity in influenza virus isolates compared to clinical specimens.influenza virus (ifv) isolates obtained from mammalian cell cultures are valuable reagents used for vaccine production, antigenic characterization, laboratory assays, and epidemiological and evolutionary studies. complete genomic comparison of ifv isolates with their original clinical specimens provides insight into cell culture-driven genomic changes which may sequentially alter the virus phenotype.201526071329
global circulation patterns of seasonal influenza viruses vary with antigenic drift.understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. the global circulation patterns of influenza a/h3n2 viruses are well characterized, but the patterns of a/h1n1 and b viruses have remained largely unexplored. here we show that the global circulation patterns of a/h1n1 (up to 2009), b/victoria, and b/yamagata viruses differ substantially from those of a/h3n2 viruses, on the basis o ...201526053121
the intranasal application of zanamivir and carrageenan is synergistically active against influenza a virus in the murine model.carrageenan is a clinically proven and marketed compound for the treatment of viral upper respiratory tract infections. as infections caused by influenza virus are often accompanied by infections with other respiratory viruses the combination of a specific anti-influenza compound with the broadly active antiviral polymer has huge potential for the treatment of respiratory infections. thus, the combination of the specific anti-influenza drug zanamivir together with carrageenan in a formulation su ...201526053018
evaluation of the zoonotic potential of a novel reassortant h1n2 swine influenza virus with gene constellation derived from multiple viral sources.in 2011-2012, contemporary north american-like h3n2 swine influenza viruses (sivs) possessing the 2009 pandemic h1n1 matrix gene (h3n2pm-like virus) were detected in domestic pigs of south korea where h1n2 siv strains are endemic. more recently, we isolated novel reassortant h1n2 sivs bearing the eurasian avian-like swine h1-like hemagglutinin and korean swine h1n2-like neuraminidase in the internal gene backbone of the h3n2pm-like virus. in the present study, we clearly provide evidence on the ...201526051886
[on-microchip pcr for detection of influenza a viruses subtypes, circulating in the human population].a oligonucleotide microchip was developed for revealing influenza a viruses subtypes, circulating in human population: pandemic h1n1 swine influenza viruses, seasonal h1n1, h2n2, h3n2, h5n1, h9n2, h7n9. typing of influenza virus was performed by on-microchip pcr. we used immobilized primers-probes selected for the neuraminidase gene that allows determining both subtype of neuraminidase and subtype of hemagglutinin.201526050481
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
[determination of influenza virus h5n1 and h7n9 using masa technology].to set up a new rapid method for the rapid determination of influenza virus h5n1 and h7n9 basing on the multi-analyte suspension array (masa) technology. sequence analysis and design of degenerate primers and specific probes were set in the comparison and analysis of h5, n1, h7 and n9 genes. in combination with masa technology, these primers and probes were used for the determination of samples of h5n1 and h7n9 and other subtypes ( h1n1, ph1n1, h5n2, h3n2 and h9n2). we developed a rapid determin ...201526951004
[development of a real-time reverse transcription pcr assay system for detection of three subtypes of influenza a and influenza b viruses].we developed the initial real-time reverse transcription pcr assay system for seasonal influenza viruses in 2011. this prototype assay system could detect and identify specific influenza a virus subtypes[h1n1, h3n2 and (h1n1) pdm09] and influenza b virus. in the 2012-2013 season, our prototype pcr assay didn't work well because of point mutations occurred in the neuraminidase (na) gene of the a (h3n2) strain. we improved the prototype assay by changing the target gene for a (h3n2) strain (2013 i ...201527089652
epidemiology of human coronavirus nl63 infection among hospitalized patients with pneumonia in taiwan.human coronavirus (hcov) nl63 is recognized in association with upper or lower respiratory tract illnesses in children. this study surveyed the prevalence of hcov-nl63 and influenza viruses in patients with influenza-like illness in taiwan during 2010-2011.201526746130
generation and characterization of monoclonal antibodies specific to avian influenza h5n1 hemagglutinin protein.highly pathogenic avian influenza (hpai) h5n1 virus has in the past breached the species barrier from infected domestic poultry to humans in close contact. although human-to-human transmission has previously not been reported, hpai h5n1 virus has pandemic potential owing to gain of function mutation(s) and/or genetic reassortment with human influenza a viruses. monoclonal antibodies (mabs) have been used for diagnosis as well as specific therapeutic candidates in several disease conditions inclu ...201526683184
prevalence of gastrointestinal symptoms in patients with influenza, clinical significance, and pathophysiology of human influenza viruses in faecal samples: what do we know?this review provides for the first time an assessment of the current understanding about the occurrence and the clinical significance of gastrointestinal (gi) symptoms in influenza patients, and their correlation with the presence of human influenza viruses in stools of patients with confirmed influenza virus infection. studies exploring how human influenza viruses spread to the patient's gi tract after a primary respiratory infection have been summarized. we conducted a systematic search of pub ...201526651485
transcription factor runx3 is induced by influenza a virus and double-strand rna and mediates airway epithelial cell apoptosis.influenza a virus (iav) targets airway epithelial cells and exploits the host cell machinery to replicate, causing respiratory illness in annual epidemics and pandemics of variable severity. the high rate of antigenic drift (viral mutation) and the putative antigenic shift (reassortant strains) have raised the need to find the host cell inducible factors modulating iav replication and its pathogenesis to develop more effective antiviral treatment. in this study, we found for the first time that ...201526643317
characterization of the localized immune response in the respiratory tract of ferrets following infection with influenza a and b viruses.the burden of infection with seasonal influenza viruses is significant. each year is typically characterized by the dominance of one (sub)type or lineage of influenza a or b virus, respectively. the incidence of disease varies annually, and while this may be attributed to a particular virus strain or subtype, the impacts of prior immunity, population differences, and variations in clinical assessment are also important. to improve our understanding of the impacts of seasonal influenza viruses, w ...201526719259
quercetin as an antiviral agent inhibits influenza a virus (iav) entry.influenza a viruses (iavs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-iav agents. the glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including a/puerto rico/8/34 (h1n1), a/fm-1/47/1 (h1n1), and a/aichi/2/68 (h3n ...201526712783
[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
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
genome-wide analysis of evolutionary markers of human influenza a(h1n1)pdm09 and a(h3n2) viruses may guide selection of vaccine strain candidates.here we analyzed whole-genome sequences of 3,969 influenza a(h1n1)pdm09 and 4,774 a(h3n2) strains that circulated during 2009-2015 in the world. the analysis revealed changes at 481 and 533 amino acid sites in proteins of influenza a(h1n1)pdm09 and a(h3n2) strains, respectively. many of these changes were introduced as a result of random drift. however, there were 61 and 68 changes that were present in relatively large number of a(h1n1)pdm09 and a(h3n2) strains, respectively, that circulated dur ...201526615216
distinct functional determinants of influenza hemagglutinin-mediated membrane fusion.membrane fusion is the critical step for infectious cell penetration by enveloped viruses. we have previously used single-virion measurements of fusion kinetics to study the molecular mechanism of influenza-virus envelope fusion. published data on fusion inhibition by antibodies to the 'stem' of influenza virus hemagglutinin (ha) now allow us to incorporate into simulations the provision that some has are inactive. we find that more than half of the has are unproductive even for virions with no ...201526613408
epidemiological analysis of influenza a infection in cambodian pigs and recommendations for surveillance strategies.this study analysed the available data of seroprevalence to human influenza viruses in pigs in cambodia using generalized linear mixed models in order to improve understanding of factors underlying the spread of human influenza viruses in cambodian pigs. the associations between seroprevalence against seasonal h1n1 influenza virus in pigs and the population density of humans and pigs were not significant. however, a positive association between anti-h3 antibodies in pigs and the human population ...201524460959
comparison between virus shedding and fever duration after treating children with pandemic a h1n1/09 and children with a h3n2 with a neuraminidase inhibitor.shedding of the pandemic virus during an influenza pandemic is thought to persist longer than shedding of influenza viruses during annual influenza seasons, because people have much less immunity against a pandemic influenza. a correlation is thought to exist between the length of virus shedding and the clinical severity of influenza illness.201524832015
live attenuated and inactivated influenza vaccines in children.live attenuated influenza vaccine (laiv) and inactivated influenza vaccine (iiv) are available for children. local and systemic immunity induced by laiv followed a month later by laiv and iiv followed by laiv were investigated with virus recovery after laiv doses as surrogates for protection against influenza on natural exposure.201525165161
targeting the ha2 subunit of influenza a virus hemagglutinin via cd40l provides universal protection against diverse subtypes.the influenza viral hemagglutinin (ha) is comprised of two subunits. current influenza vaccine predominantly induces neutralizing antibodies (abs) against the ha1 subunit, which is constantly evolving in unpredictable fashion. the other subunit, ha2, however, is highly conserved but largely shielded by the ha head domain. thus, enhancing immune response against ha2 could potentially elicit broadly inhibitory abs. we generated a recombinant adenovirus (rad) encoding secreted fusion protein, consi ...201525052763
h3n2 canine influenza virus with the matrix gene from the pandemic a/h1n1 virus: infection dynamics in dogs and ferrets.after an outbreak of pandemic influenza a/h1n1 (ph1n1) virus, we had previously reported the emergence of a recombinant canine influenza virus (civ) between the ph1n1 virus and the classic h3n2 civ. our ongoing routine surveillance isolated another reassortant h3n2 civ carrying the matrix gene of the ph1n1 virus from 2012. the infection dynamics of this h3n2 civ variant (civ/h3n2mv) were investigated in dogs and ferrets via experimental infection and transmission. the civ/h3n2mv-infected dogs an ...201524977303
serological and virological surveillance of avian influenza a virus h9n2 subtype in humans and poultry in shanghai, china, between 2008 and 2010.we report the serological evidence of low-pathogenic avian influenza (lpai) h9n2 infection in an occupational poultry-exposed population and a general population. a serological survey of an occupational poultry-exposed population and a general population was conducted using a haemagglutinin-inhibiting (hi) assay in shanghai, china, from january 2008 to december 2010. evidence of higher anti-h9 antibodies was found in serum samples collected from poultry workers. during this period, 239 h9n2 avia ...201524803167
prediction of the next highly pathogenic avian influenza pandemic that can cause illness in humans.in recent years, avian influenza viruses (aivs) have seriously threatened human health. questions such as: why do aivs infect humans?, how quickly can an aiv become pandemic?, and which virus is the most dangerous? cannot be sufficiently answered using current bioinformatic studies.201526612517
a single dose of an avian h3n8 influenza virus vaccine is highly immunogenic and efficacious against a recently emerged seal influenza virus in mice and ferrets.h3n8 influenza viruses are a commonly found subtype in wild birds, usually causing mild or no disease in infected birds. however, they have crossed the species barrier and have been associated with outbreaks in dogs, pigs, donkeys, and seals and therefore pose a threat to humans. a live attenuated, cold-adapted (ca) h3n8 vaccine virus was generated by reverse genetics using the wild-type (wt) hemagglutinin (ha) and neuraminidase (na) genes from the a/blue-winged teal/texas/sg-00079/2007 (h3n8) ( ...201525903333
the avian-origin pb1 gene segment facilitated replication and transmissibility of the h3n2/1968 pandemic influenza virus.the h2n2/1957 and h3n2/1968 pandemic influenza viruses emerged via the exchange of genomic rna segments between human and avian viruses. the avian hemagglutinin (ha) allowed the hybrid viruses to escape preexisting immunity in the human population. both pandemic viruses further received the pb1 gene segment from the avian parent (y. kawaoka, s. krauss, and r. g. webster, j virol 63:4603-4608, 1989), but the biological significance of this observation was not understood. to assess whether the avi ...201525631088
new reassortant and enzootic european swine influenza viruses transmit efficiently through direct contact in the ferret model.the reverse zoonotic events that introduced the 2009 pandemic influenza virus into pigs have drastically increased the diversity of swine influenza viruses in europe. the pandemic potential of these novel reassortments is still unclear, necessitating enhanced surveillance of european pigs with additional focus on risk assessment of these new viruses. in this study, four european swine influenza viruses were assessed for their zoonotic potential. two of the four viruses were enzootic viruses of s ...201525701826
[infectivity titers of each component of the influenza virus in the live vaccine purchased from a parallel import distributing system].currently in japan, the only approved influenza vaccine is the inactivated vaccine which is injected subcutaneously. on the other hand, there is a live vaccine available elsewhere in the world. flumist, an intranasal influenza live vaccine which contains four strains of infectious viruses, has been used in the united states for more than 10 years; the vaccine has been found effective in clinical trials, while it has some limitations such as those on subjects for the administration, strict storag ...201526821520
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
evolution of 2014/15 h3n2 influenza viruses circulating in us: consequences for vaccine effectiveness and possible new pandemic.a key factor in the effectiveness of the seasonal influenza vaccine is its immunological compatibility with the circulating viruses during the season. here we propose a new bioinformatics approach for analysis of influenza viruses which could be used as an efficient tool for selection of vaccine viruses, assessment of the effectiveness of seasonal influenza vaccines, and prediction of the epidemic/pandemic potential of novel influenza viruses.201526733989
[analysis of the neuraminidase amino acid sequences of influenza a/h1n1pdm09, a/h3n2, and b viruses isolated from influenza patients in the 2013/14 japanese influenza season].neuraminidase (na) is an essential surface protein for influenza virus replication. na inhibitors are commonly used for the treatment of influenza patients in japan. several mutations that reduce the effect of na inhibitors have been reported. we sequenced the whole na segment of isolated virus from influenza patients and investigated the relation between the na amino acid sequence and the 50% inhibitory concentration (ic50) of four na inhibitors.201526630841
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 ...201526629625
natural co-infection of influenza a/h3n2 and a/h1n1pdm09 viruses resulting in a reassortant a/h3n2 virus.despite annual co-circulation of different subtypes of seasonal influenza, co-infections between different viruses are rarely detected. these co-infections can result in the emergence of reassortant progeny.201526590689
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
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
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
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
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
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
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
[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
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
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
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
analytical sensitivity comparison between singleplex real-time pcr and a multiplex pcr platform for detecting respiratory viruses.multiplex pcr methods are attractive to clinical laboratories wanting to broaden their detection of respiratory viral pathogens in clinical specimens. however, multiplexed assays must be well optimized to retain or improve upon the analytic sensitivity of their singleplex counterparts. in this experiment, the lower limit of detection (lod) of singleplex real-time pcr assays targeting respiratory viruses is compared to an equivalent panel on a multiplex pcr platform, the genmark esensor rvp. lods ...201526569120
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
[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
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
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
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
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
human mir-3145 inhibits influenza a viruses replication by targeting and silencing viral pb1 gene.micrornas (mirnas) play an important role in the regulation of gene expression and are involved in many cellular processes including inhibition of viral replication in infected cells. in this study, three subtypes of influenza a viruses (ph1n1, h5n1 and h3n2) were analyzed to identify candidate human mirnas targeting and silencing viral genes expression. candidate human mirnas were predicted by mirbase and rnahybrid based on minimum free energy (mfe) and hybridization patterns between human mirn ...201526080461
swine influenza a(h3n2) virus infection in immunocompromised man, italy, 2014.because swine influenza virus infection is seldom diagnosed in humans, its frequency might be underestimated. we report a immunocompromised hematologic patient with swine influenza a(h3n2) virus in 2014 in italy. local pigs were the source of this human infection.201526079745
quantitative analysis of influenza a (h3n2) e119v and r292k variants in clinical specimens by real-time reverse transcription polymerase chain reaction.because influenza virus isolates after cell culture are required to determine their susceptibility to neuraminidase inhibitors, the differences in normal or low-susceptibility variant population frequencies between clinical samples and isolates have not been considered.201526071346
abnormal expressions of inflammatory-related mediators and inhibition of fat metabolism in mice infected with influenza a virus.the pathophysiological role of influenza infection is poorly understood. in this study, one non-neurovirulent virus (iav/aichi/2/68/h3n2) strain was used to infect intra-nasally mice at different age to investigate the mechanism of cerebral edema formation and lower activities of mitochondria enzymes after influenza a virus (iav) infection. mice suffered 46.4% mortality in newborn compared with 96.0% in weanling, 100% in adult on day 7, respectively. iav-rna was easily detected in the brain of n ...201526051732
influenza a virus coinfection through transmission can support high levels of reassortment.the reassortment of gene segments between influenza viruses increases genomic diversity and plays an important role in viral evolution. we have shown previously that this process is highly efficient within a coinfected cell and, given synchronous coinfection at moderate or high doses, can give rise to ~60 to 70% of progeny shed from an animal host. conversely, reassortment in vivo can be rendered undetectable by lowering viral doses or extending the time between infections. one might also predic ...201526041285
the effects of h3n2 swine influenza virus infection on tlrs and rlrs signaling pathways in porcine alveolar macrophages.swine influenza is an economically important respiratory disease of swine resulting from infection with influenza a virus. swine influenza virus (siv) becomes the focus as pigs have been hypothesized to serve as an intermediate host for the adaptation of avian influenza viruses to humans or as mixing vessels for the generation of genetically reassortant viruses. the ability of the innate immune system to detect and respond to pathogens is important for survival. therefore, there is a critical ne ...201526021751
[virological characteristics of influenza a (h3n2) virus in mainland china during 2013-2014].to analyze the antigenic and genetic characteristics of the influenza a (h3n2) virus in mainland china during the surveillance year of 2013-2014, the antigenic characteristics of h3n2 virus were analyzed using reference ferret anti-sera. the nucleotide sequences of the viruses were determined by sanger dideoxy sequencing, phylogenetic trees were constructed with the neighbor-joining method, and the genetic characteristics of the viruses were determined in comparison to current vaccine strains. t ...201525997327
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