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serial intervals of respiratory infectious diseases: a systematic review and analysis.the serial interval of an infectious disease represents the duration between symptom onset of a primary case and symptom onset of its secondary cases. a good evidence base for such values is essential, because they allow investigators to identify epidemiologic links between cases and serve as an important parameter in epidemic transmission models used to design infection control strategies. we reviewed the literature for available data sets containing serial intervals and for reported values of ...201425294601
serological evidence for influenza virus infection in korean wild boars.serum samples from 1,011 wild boars hunted in 2012 were collected for serological surveillance for 4 subtypes (pandemic a (h1n1) 2009 and classical h1n1, h1n2 and h3n2) of swine influenza virus (siv). samples from 12 of the boars were identified as positive for siv (pandemic a (h1n1) 2009, n=9; classical h1n1, n=2; and h1n2, n=1) by a hemagglutination inhibition test (hi test) and a nucleoprotein (np)-based enzyme-linked immunosorbent assay (np-elisa). although the overall seroprevalence of siv ...201425298239
characterization of human influenza viruses in lebanon during 2010-2011 and 2011-2012 post-pandemic seasons.to genetically characterize human influenza viruses and their susceptibilities to antivirals during two post-pandemic seasons in lebanon.201425301400
canine susceptibility to human influenza viruses (a/pdm 09h1n1, a/h3n2 and b).we investigated the infectivity and transmissibility of the human seasonal h3n2, pandemic (pdm) h1n1 (2009) and b influenza viruses in dogs. dogs inoculated with human seasonal h3n2 and pdm h1n1 influenza viruses exhibited nasal shedding and were seroconverted against the viruses; this did not occur in the influenza b virus-inoculated dogs. transmission of human h3n2 virus between dogs was demonstrated by observing nasal shedding and seroconversion in naïve dogs after contact with inoculated dog ...201525312584
ifitm3 polymorphism rs12252-c restricts influenza a viruses.the ifitm3 polymorphism rs12252-c, which encodes an ifitm3 isoform (δ21 ifitm3) lacking 21 amino acids at the amino terminus, has been controversially associated with poor clinical outcomes in patients with h1n1 influenza a virus (iav) infections. in vitro studies have shown that δ21 ifitm3 loses its ability to restrict h1n1 iav. subsequent research has also revealed that tyrosine 20 is the key determinant for ifitm3 endocytic trafficking, which is essential for the efficient anti-viral activity ...201425314048
variations in ph sensitivity, acid stability, and fusogenicity of three influenza virus h3 subtypes.influenza a virus strains adapt to achieve successful entry into host species. entry is mediated by the viral membrane protein hemagglutinin (ha), which triggers membrane fusion and genome release under acidic conditions in the endosome. in addition to changes in the receptor binding domain, the acid stability of ha has been linked to the successful transmission of virus between avian and human hosts. however, to fully understand the connection between changes in ha and host tropism, additional ...201425320308
polymerase discordance in novel swine influenza h3n2v constellations is tolerated in swine but not human respiratory epithelial cells.swine-origin h3n2v, a variant of h3n2 influenza virus, is a concern for novel reassortment with circulating pandemic h1n1 influenza virus (h1n1pdm09) in swine because this can lead to the emergence of a novel pandemic virus. in this study, the reassortment prevalence of h3n2v with h1n1pdm09 was determined in swine cells. reassortants evaluated showed that the h1n1pdm09 polymerase (pa) segment occurred within swine h3n2 with ∼ 80% frequency. the swine h3n2-human h1n1pdm09 pa reassortant (swh3n2-h ...201425330303
[ph-dependent rearrangements in the influenza a virus].the influenza virus possesses two modules: internal ribonucleoprotein (rnp) containing the viral genome rna and external lipid envelope with transmembrane ionic channel protein m2 and embedded glycoproteins hemagglutinin (ha) and neuraminidase (na) forming surface spike ends. these modules are combined in a whole virion by the matrix protein m1. the effect of the acidic ph 4,2-4,5 on the influenza virus grown in mdck-h cells was tested. the a/aichi/68 (h3n2) virus synthesized in mdck-h cells was ...201625335418
epidemiological and virological characteristics of influenza viruses circulating in cambodia from 2009 to 2011.the cambodian national influenza center (nic) monitored and characterized circulating influenza strains from 2009 to 2011.201425340711
respiratory viruses and bacteria among pilgrims during the 2013 hajj.pilgrims returning from the hajj might contribute to international spreading of respiratory pathogens. nasal and throat swab specimens were obtained from 129 pilgrims in 2013 before they departed from france and before they left saudi arabia, and tested by pcr for respiratory viruses and bacteria. overall, 21.5% and 38.8% of pre-hajj and post-hajj specimens, respectively, were positive for ≥1 virus (p = 0.003). one third (29.8%) of the participants acquired ≥1 virus, particularly rhinovirus (14. ...201425341199
safety and immunogenicity of a novel cold-adapted modified-live equine influenza virus vaccine.to design and evaluate the safety and immunogenicity of a modified-live vaccine to prevent equine influenza virus (eiv) infection based on the novel reassortant cold-adapted strain a/hk/otar/6:2/2010.201425348146
antigenic and genomic characterization of human influenza a and b viruses circulating in argentina after the introduction of influenza a(h1n1)pdm09.this study was conducted as part of the argentinean influenza and other respiratory viruses surveillance network, in the context of the global influenza surveillance carried out by the world health organization (who). the objective was to study the activity and the antigenic and genomic characteristics of circulating viruses for three consecutive seasons (2010, 2011 and 2012) in order to investigate the emergence of influenza viral variants. during the study period, influenza virus circulation w ...201425351708
detection of novel reassortant influenza a (h3n2) and h1n1 2009 pandemic viruses in swine in hanoi, vietnam.from may to september 2013, monthly samples were collected from swine in a vietnamese slaughterhouse for influenza virus isolation and serological testing. a(h1n1)pdm09 viruses and a novel h3n2 originating from reassortment between a(h1n1)pdm09 and novel viruses of the north american triple reassortant lineage were isolated. serological results showed low seroprevalence for the novel h3n2 virus and higher seroprevalence for a(h1n1)pdm09 viruses. in addition, serology suggested that other swine i ...201525363845
multiplex rt-pcr and indirect immunofluorescence assays for detection and subtyping of human influenza virus in tunisia.influenza viruses are negative stranded segmented rna viruses belonging to orthomyxoviridae family. they are classified into three types a, b, and c. type a influenza viruses are classified into subtypes according to the antigenic characters of the surface glycoproteins: hemagglutinin (h) and neuraminidase (n). the aim of the present study is to develop a fast and reliable multiplex rt-pcr technique for detecting simultaneously the subtypes a/h1n1 and a/h3n2 of influenza virus. our study include ...201525366277
non-avian animal reservoirs present a source of influenza a pb1-f2 proteins with novel virulence-enhancing markers.pb1-f2 protein, expressed from an alternative reading frame of most influenza a virus (iav) pb1 segments, may possess specific residues associated with enhanced inflammation (l62, r75, r79, and l82) and cytotoxicity (i68, l69, and v70). these residues were shown to increase the pathogenicity of primary viral and secondary bacterial infections in a mouse model. in contrast to human seasonal influenza strains, virulence-associated residues are present in pb1-f2 proteins from pandemic h1n1 1918, h2 ...201425368997
predicting evolution from the shape of genealogical trees.given a sample of genome sequences from an asexual population, can one predict its evolutionary future? here we demonstrate that the branching patterns of reconstructed genealogical trees contains information about the relative fitness of the sampled sequences and that this information can be used to predict successful strains. our approach is based on the assumption that evolution proceeds by accumulation of small effect mutations, does not require species specific input and can be applied to a ...201425385532
substrate specificity of avian influenza h5n1 neuraminidase.to characterise neuraminidase (na) substrate specificity of avian influenza h5n1 strains from humans and birds comparing to seasonal influenza virus.201425396120
comparative mutational analyses of influenza a viruses.the error-prone rna-dependent rna polymerase (rdrp) and external selective pressures are the driving forces for rna viral diversity. when confounded by selective pressures, it is difficult to assess if influenza a viruses (iav) that have a wide host range possess comparable or distinct spontaneous mutational frequency in their rdrps. we used in-depth bioinformatics analyses to assess the spontaneous mutational frequencies of two rdrps derived from human seasonal (a/wuhan/359/95; wuhan) and h5n1 ...201525404565
field study on swine influenza virus (siv) infection in weaner pigs and sows.the aim of this field study was to explore the occurrence of and factors associated with the detection of swine influenza virus (siv) by rtqpcr in weaner pigs and sows from herds with a history of respiratory or reproductive disorders.201425405955
influenza vaccine effectiveness in the united states during 2012-2013: variable protection by age and virus type.during the 2012-2013 influenza season, there was cocirculation of influenza a(h3n2) and 2 influenza b lineage viruses in the united states.201525406334
the k526r substitution in viral protein pb2 enhances the effects of e627k on influenza virus replication.host-adaptive strategies, such as the e627k substitution in the pb2 protein, are critical for replication of avian influenza a viruses in mammalian hosts. here we show that mutation pb2-k526r is present in some human h7n9 influenza isolates, in nearly 80% of h5n1 human isolates from indonesia and, in conjunction with e627k, in almost all seasonal h3n2 viruses since 1970. polymerase complexes containing pb2-526r derived from h7n9, h5n1 or h3n2 viruses exhibit increased polymerase activity. pb2-52 ...201425409547
antibody landscapes after influenza virus infection or vaccination.we introduce the antibody landscape, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among pathogen strains. we generated antibody landscapes to study immune profiles covering 43 years of influenza a/h3n2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. upon infection and vaccination, titers increased broadly, including ...201425414313
molecular characterization of h3n2 influenza a viruses isolated from ontario swine in 2011 and 2012.data about molecular diversity of commonly circulating type a influenza viruses in ontario swine are scarce. yet, this information is essential for surveillance of animal and public health, vaccine updates, and for understanding virus evolution and its large-scale spread.201425416300
influenza pneumonia surveillance among hospitalized adults may underestimate the burden of severe influenza disease.studies seeking to estimate the burden of influenza among hospitalized adults often use case definitions that require presence of pneumonia. the goal of this study was to assess the extent to which restricting influenza testing to adults hospitalized with pneumonia could underestimate the total burden of hospitalized influenza disease.201425423025
poly i:c adjuvanted inactivated swine influenza vaccine induces heterologous protective immunity in pigs.swine influenza is widely prevalent in swine herds in north america and europe causing enormous economic losses and a public health threat. pigs can be infected by both avian and mammalian influenza viruses and are sources of generation of reassortant influenza viruses capable of causing pandemics in humans. current commercial vaccines provide satisfactory immunity against homologous viruses; however, protection against heterologous viruses is not adequate. in this study, we evaluated the protec ...201525437101
continued effectiveness of laninamivir octanate hydrate for influenza treatment in japan: comparison between the 2011-2012 and 2012-2013 influenza seasons.the clinical effectiveness of laninamivir octanoate hydrate (laninamivir) was investigated in the japanese 2012-2013 influenza season for comparison with that of the japanese 2011-2012 influenza season. a total of 235 patients were enrolled, of whom 210 were evaluated for the duration of fever and other symptoms. the median durations of fever for a(h3n2) were 32.0 and 38.0 h and the median durations of symptoms for the a(h3n2) were 102.0 and 84.0 h for patients aged under 10 and 10 years or olde ...201425444677
baicalin inhibits autophagy induced by influenza a virus h3n2.baicalin, a natural product isolated from scutellariaradix, has been reported to have significant in vivo and in vitro anti-influenza virus activity, but the underlying mechanism remains poorly understood. in this study, we found that baicalin inhibited autophagy induced by influenza virus a3/beijing/30/95 (h3n2) in both a549 and ana-1 cells. the results showed that h3n2 induced autophagy by suppressing mtor signaling pathway, which however could be significantly inhibited by baicalin. baicalin ...201525446340
progressive antigenic drift and phylogeny of human influenza a(h3n2) virus over five consecutive seasons (2009-2013) in hangzhou, china.vaccine efficacy (ve) can be affected by progressive antigenic drift or any new reassortment of influenza viruses. to effectively track the evolution of human influenza a(h3n2) virus circulating in hangzhou, china, a total of 65 clinical specimens were selected randomly from outpatients infected by a(h3n2) viruses during the study period from november 2009 to december 2013. the results of reduced ve and antigenic drift of the correspondent epitopes (c-d-e to a-b) suggest that the current vaccine ...201425447724
a vero-cell-adapted vaccine donor strain of influenza a virus generated by serial passages.a cell culture-based vaccine production system is preferred for the large-scale production of influenza vaccines and has advantages for generating vaccines against highly pathogenic influenza a viruses. vero cells have been widely used in human vaccine manufacturing, and the safety of these cells has been well demonstrated. however, the most commonly used influenza-vaccine donor virus, a/puerto rico/8/1934 (pr8) virus, does not grow efficiently in vero cells. therefore, we adapted the pr8 virus ...201525448099
synergistic effect of nitazoxanide with neuraminidase inhibitors against influenza a viruses in vitro.the emergence of drug-resistant influenza a virus (iav) strains represents a serious threat to global human health and underscores the need for novel approaches to anti-influenza chemotherapy. combination therapy with drugs affecting different iav targets represents an attractive option for influenza treatment. we have previously shown that the thiazolide anti-infective nitazoxanide (ntz) inhibits h1n1 iav replication by selectively blocking viral hemagglutinin maturation. herein we investigate ...201525451059
drug susceptibility of influenza a/h3n2 strains co-circulating during 2009 influenza pandemic: first report from mumbai.from its first instance in 1977, resistance to amantadine, a matrix (m2) inhibitor has been increasing among influenza a/h3n2, thus propelling the use of oseltamivir, a neuraminidase (na) inhibitor as a next line drug. information on drug susceptibility to amantadine and neuraminidase inhibitors for influenza a/h3n2 viruses in india is limited with no published data from mumbai. this study aimed at examining the sensitivity to m2 and na inhibitors of influenza a/h3n2 strains isolated from 2009 t ...201525461259
efficient replication and strong induction of innate immune responses by h9n2 avian influenza virus in human dendritic cells.avian influenza a (h9n2) viruses have occasionally been identified in humans with upper respiratory tract infections. the novel h7n9/2013 virus identified in china shows that a low pathogenic avian influenza (lpai) virus can be highly pathogenic in humans. therefore, it is important to understand virus-host cell interactions and immune responses triggered by lpai viruses in humans. we found that lpai a/hong kong/1073/99 (h9n2) virus replicated efficiently in human dendritic cells (dcs). the h9n2 ...201425461529
combination of multiplex reverse-transcription loop-mediated isothermal amplification with an immunochromatographic strip for subtyping influenza a virus.considering the fatal human victims and economic loss by the annual epidemic influenza virus, the development of a rapid and convenient genetic analysis methodology is demanding for timely on-site pathogen detection. in this study, we utilized reverse-transcription loop-mediated isothermal amplification (rt-lamp) for multiplex target gene amplification, and the resultant amplicons were analyzed on the immunochromatographic strip (ics) for subtyping influenza a virus. through the optimized primer ...201525467501
novel triple reassortant h1n2 influenza viruses bearing six internal genes of the pandemic 2009/h1n1 influenza virus were detected in pigs in china.the pandemic a/h1n1 influenza viruses emerged in both mexico and the united states in march 2009, and were transmitted efficiently in the human population. transmissions of the pandemic 2009/h1n1 virus from humans to poultry and other species of mammals were reported from several continents during the course of the 2009 h1n1 pandemic. reassortant h1n1, h1n2, and h3n2 viruses containing genes of the pandemic 2009/h1n1 viruses appeared in pigs in some countries.201425467861
flipping in the pore: discovery of dual inhibitors that bind in different orientations to the wild-type versus the amantadine-resistant s31n mutant of the influenza a virus m2 proton channel.influenza virus infections lead to numerous deaths and millions of hospitalizations each year. one challenge facing anti-influenza drug development is the heterogeneity of the circulating influenza viruses, which comprise several strains with variable susceptibility to antiviral drugs. for example, the wild-type (wt) influenza a viruses, such as the seasonal h1n1, tend to be sensitive to antiviral drugs, amantadine and rimantadine, while the s31n mutant viruses, such as the pandemic 2009 h1n1 (h ...201425470189
computational insights into the inhibition of influenza viruses by rupestonic acid derivatives: pharmacophore modeling, 3d-qsar, comfa and comsia studies.the pharmacophore modeling and 3d-qsar studies were performed on a series of amino alkyl rupestonates (rupestonic acid) derivatives reported for h1n1, h3n2 and influenza b virus, na inhibition. in order to improve the efficacy of amino alkyl rupestonates derivatives, a four point pharmacophore model with one acceptor and three hydrophobic regions was developed. furthermore, the 3d-qsar model was generated based on the pharmacophore hypothesis (ahhh) for each subtype. the hypothesis was more sign ...201525483013
ten years (2004-2014) of influenza surveillance in northern italy.as the regional influenza reference centre operating within the italian network influnet, here we report data on virological and epidemiological surveillance of influenza, as well as on the vaccination coverage rates achieved in lombardy (northern italy) over 10 consecutive winter seasons (2004-2014).   over the past 10 years, influenza vaccine coverage declined both in the general population (from 15.7% in 2004-2005 to 11.7% in 2013-2014) and in the vaccine-target population of individuals ≥65- ...201525483536
influenza vaccine effectiveness assessment through sentinel virological data in three post-pandemic seasons.influenza vaccination aims at reducing the incidence of serious disease, complications and death among those with the most risk of severe influenza disease. influenza vaccine effectiveness (ve) through sentinel surveillance data from the pidirac program (daily acute respiratory infection surveillance of catalonia) during 2010-2011, 2011-2012, and 2012-2013 influenza seasons, with three different predominant circulating influenza virus (iv) types [a(h1n1)pdm09, a(h3n2) and b, respectively] was as ...201525483540
episodic nucleotide substitutions in seasonal influenza virus h3n2 can be explained by stochastic genealogical process without positive selection.nucleotide substitutions in the ha1 domain of seasonal influenza virus h3n2 occur in temporal clusters, which was interpreted as a result of recurrent selective sweeps underlying antigenic drift. however, classical theory by watterson suggests that episodic substitutions are mainly due to stochastic genealogy combined with unique genetic structure of influenza virus: high mutation rate over a nonrecombining viral segment. this explains why even larger variance in the number of allelic fixations ...201525492497
chimeric neuraminidase and mutant pb1 gene constellation improves growth and yield of h5n1 vaccine candidate virus.we previously showed that a mutated pb1 gene improved the growth kinetics of a h3n2 influenza reassortant. here, we showed that the same mutations improved the growth kinetics of a virus containing the a/vietnam/1203/2004 (h5n1) haemagglutinin and neuraminidase (na). total protein yield and na activity were increased when a chimeric na was included. these increases indicated that the synergistic effect was due to the gene constellation containing both the altered pb1 gene and the chimeric na gen ...201525502649
[ability of the influenza viruses and their envelope proteins to stimulates endothelial cells apoptosis in vitro].the ability of the modern epidemic strains of influenza virus type a (subtypes h5n1, h3n2, h1n1pdm) and their surface proteins, hemagglutinin (ha) and neuraminidase to cause the activation of the cellular protein caspase-3 and stimulate the emergence of phosphatidylserine on the membrane of human endothelial cell line eahy926 has been studied. it was questioned how the viruses and their surface proteins that were studied cause the activation of caspase-3 after 0.5 h of exposure that recorded imm ...201325509110
cross-reactive immunity against influenza viruses in children and adults following 2009 pandemic h1n1 infection.2009 h1n1 pandemic influenza (a(h1n1)pdm09) virus infected large numbers of people worldwide. recent studies suggest infection with a(h1n1)pdm09 virus elicited cross-reactive anti-hemagglutinin (ha) memory b cell response to conserved regions of ha. however, the breadth and magnitude of cross-reactive immunity in children and adults following a(h1n1)pdm09 infection are unknown.201525513756
safety and immunogenicity of cell culture-derived a/h3n2 variant influenza vaccines: a phase i randomized, observer-blind, dose-ranging study.a/h3n2 variant (h3n2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important.201525538277
pathogenicity and transmissibility of novel reassortant h3n2 influenza viruses with 2009 pandemic h1n1 genes in pigs.at least 10 different genotypes of novel reassortant h3n2 influenza viruses with 2009 pandemic h1n1 [a(h1n1)pdm09] gene(s) have been identified in u.s. pigs, including the h3n2 variant with a single a(h1n1)pdm09 m gene, which has infected more than 300 people. to date, only three genotypes of these viruses have been evaluated in animal models, and the pathogenicity and transmissibility of the other seven genotype viruses remain unknown. here, we show that three h3n2 reassortant viruses that cont ...201525540372
european surveillance network for influenza in pigs: surveillance programs, diagnostic tools and swine influenza virus subtypes identified in 14 european countries from 2010 to 2013.swine influenza causes concern for global veterinary and public health officials. in continuing two previous networks that initiated the surveillance of swine influenza viruses (sivs) circulating in european pigs between 2001 and 2008, a third european surveillance network for influenza in pigs (esnip3, 2010-2013) aimed to expand widely the knowledge of the epidemiology of european sivs. esnip3 stimulated programs of harmonized siv surveillance in european countries and supported the coordinatio ...201425542013
detection of influenza antigenic variants directly from clinical samples using polyclonal antibody based proximity ligation assays.identification of antigenic variants is the key to a successful influenza vaccination program. the empirical serological methods to determine influenza antigenic properties require viral propagation. here a novel quantitative pcr-based antigenic characterization method using polyclonal antibody and proximity ligation assays, or so-called polypla, was developed and validated. this method can detect a viral titer that is less than 1000 tcid50/ml. not only can this method differentiate between diff ...201525546251
comparison of multiplex rt-pcr with virus isolation for detection, typing and sub-typing of influenza virus from influenza-like illness cases.influenza epidemics and periodic pandemics occur worldwide resulting in significant mortality, morbidity and economic loss. there is need for a sensitive, rapid and cost-effective assay to detect, type and sub-type influenza viruses, as cell culture has a long turnaround time.201525560005
integrated centrifugal reverse transcriptase loop-mediated isothermal amplification microdevice for influenza a virus detection.an integrated reverse transcriptase loop-mediated isothermal amplification (rt-lamp) microdevice which consists of microbead-assisted rna purification and rt-lamp with real-time monitoring by a miniaturized optical detector was demonstrated. the integrated rt-lamp microdevice includes four reservoirs for a viral rna sample (purified influenza a viral rna or lysates), a washing solution (70% ethanol), an elution solution (rnase-free water), and an rt-lamp cocktail, and two chambers (a waste chamb ...201525569879
serological evidence of avian influenza virus and canine influenza virus infections among stray cats in live poultry markets, china.from january 2010 to january 2012, we collected sera samples from 700 stray cats living in close proximity to poultry farms or poultry markets in 4 provinces in china. a number of cats had evidence of avian and canine influenza virus infection: avian h9n2 [24 by hi ≥1:20 and 16 by microneutralization (mn) assay ≥1:80]; avian h5n1 (9 by hi ≥1:20 and 3 by mn assay ≥1:80) and canine h3n2 (32 by hi ≥1:20 and 18 by mn ≥1:80). bivariate analyses revealed that cats sampled near live poultry markets and ...201525575880
detection of a transient r292k mutation in influenza a/h3n2 viruses shed for several weeks by an immunocompromised patient.we describe the case of an immunocompromised patient, positive for influenza a virus (h3n2), in whom the neuraminidase r292k mutation was transiently detected during oseltamivir treatment. the r292k mutation was identified by direct testing in 3 of 11 respiratory specimens collected throughout the patient's illness but in none of the cultures from those specimens.201525588658
effective lethal mutagenesis of influenza virus by three nucleoside analogs.lethal mutagenesis is a broad-spectrum antiviral strategy that exploits the high mutation rate and low mutational tolerance of many rna viruses. this approach uses mutagenic drugs to increase viral mutation rates and burden viral populations with mutations that reduce the number of infectious progeny. we investigated the effectiveness of lethal mutagenesis as a strategy against influenza virus using three nucleoside analogs, ribavirin, 5-azacytidine, and 5-fluorouracil. all three drugs were acti ...201525589650
early estimates of seasonal influenza vaccine effectiveness - united states, january 2015.in the united states, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months. each season since 2004-05, cdc has estimated the effectiveness of seasonal influenza vaccine in preventing medically attended acute respiratory illness (ari) associated with laboratory-confirmed influenza. this season, early estimates of influenza vaccine effectiveness are possible because of widespread, early circulation of influenza viruses. by january 3, 2015, 46 states were expe ...201525590680
influenza viruses with receptor-binding n1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice.in nearly all characterized influenza viruses, hemagglutinin (ha) is the receptor-binding protein while neuraminidase (na) is a receptor-cleaving protein that aids in viral release. however, in recent years, several groups have described point mutations that confer receptor-binding activity on na, albeit in laboratory rather than natural settings. one of these mutations, d151g, appears to arise in the na of recent human h3n2 viruses upon passage in tissue culture. we inadvertently isolated the s ...201525609803
identification of pb2 mutations responsible for the efficient replication of h5n1 influenza viruses in human lung epithelial cells.highly pathogenic h5n1 avian influenza viruses have caused outbreaks among poultry worldwide, resulting in sporadic infections in humans with approximately 60% mortality. however, efficient transmission of h5n1 viruses among humans has yet to occur, suggesting that further adaptation of h5n1 viruses to humans is required for their efficient transmission among humans. the viral determinants for efficient replication in humans are currently poorly understood. here, we report that the polymerase pb ...201525609813
2012/13 influenza vaccine effectiveness against hospitalised influenza a(h1n1)pdm09, a(h3n2) and b: estimates from a european network of hospitals.while influenza vaccines aim to decrease the incidence of severe influenza among high-risk groups, evidence of influenza vaccine effectiveness (ive) among the influenza vaccine target population is sparse. we conducted a multicentre test-negative case-control study to estimate ive against hospitalised laboratory-confirmed influenza in the target population in 18 hospitals in france, italy, lithuania and the navarre and valencia regions in spain. all hospitalised patients aged ≥18 years, belongin ...201525613779
structure and receptor binding preferences of recombinant human a(h3n2) virus hemagglutinins.a(h3n2) influenza viruses have circulated in humans since 1968, and antigenic drift of the hemagglutinin (ha) protein continues to be a driving force that allows the virus to escape the human immune response. since the major antigenic sites of the ha overlap into the receptor binding site (rbs) of the molecule, the virus constantly struggles to effectively adapt to host immune responses, without compromising its functionality. here, we have structurally assessed the evolution of the a(h3n2) viru ...201525617824
whole-genome sequences of influenza a(h3n2) viruses isolated from brazilian patients with mild illness during the 2014 season.the influenza a(h3n2) virus has circulated worldwide for almost five decades and is the dominant subtype in most seasonal influenza epidemics, as occurred in the 2014 season in south america. in this study we evaluate five whole genome sequences of influenza a(h3n2) viruses detected in patients with mild illness collected from january-march 2014. to sequence the genomes, a new generation sequencing (ngs) protocol was performed using the ion torrent pgm platform. in addition to analysing the comm ...201525626457
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
serological evidence of pandemic (h1n1) 2009 virus in pigs, west and central africa.besides birds, pigs are another important reservoir of influenza a viruses that can be transmitted to human, as highlighted by the emergence and spread of the pandemic (h1n1) virus (pdm/09) in 2009. surveillance in pigs is therefore necessary for public health and influenza pandemic preparedness. nevertheless, there is a serious lack of data on influenza in africa, especially in swine. we therefore collected serum samples from pigs in nigeria (2009, 2012) and cameroon (2011) in which the presenc ...201525631252
limited effect of recombinant human mannose-binding lectin on the infection of novel influenza a (h7n9) virus in vitro.mannose-binding lectin (mbl), a pattern-recognition molecule in serum, recognizes specific hexose sugars rich in mannose and n-acetylglucosamine on bacterium, yeasts, viruses as well as apoptotic cells. it has been well-identified that mbl has antiviral effects via binding to seasonal influenza h1 and h3 subtype viruses. influenza a (h7n9) virus, a novel reassortant virus to human population, possesses the surface hemagglutinin (ha) and neuraminidase (na) genes from duck and wild-bird influenza ...201525634695
molecular surveillance of antiviral drug resistance of influenza a/h3n2 virus in singapore, 2009-2013.adamantanes and neuraminidase inhibitors (nais) are two classes of antiviral drugs available for the chemoprophylaxis and treatment of influenza infections. to determine the frequency of drug resistance in influenza a/h3n2 viruses in singapore, large-scale sequencing of neuraminidase (na) and matrix protein (mp) genes was performed directly without initial culture amplification. 241 laboratory-confirmed influenza a/h3n2 clinical samples, collected between may 2009 and november 2013 were included ...201525635767
emergence of human-like h3n2 influenza viruses in pet dogs in guangxi, china.after the 1968 h3n2 pandemic emerged in humans, h3n2 influenza viruses continuously circulated and evolved in nature. an h3n2 variant was circulating in humans in the 1990s and subsequently introduced into the pig population in the 2000s. this virus gradually became the main subtype of swine influenza virus worldwide. however, there were no reports of infections in dogs with this virus.201525645259
physical detection of influenza a epitopes identifies a stealth subset on human lung epithelium evading natural cd8 immunity.vaccines eliciting immunity against influenza a viruses (iavs) are currently antibody-based with hemagglutinin-directed antibody titer the only universally accepted immune correlate of protection. to investigate the disconnection between observed cd8 t-cell responses and immunity to iav, we used a poisson liquid chromatography data-independent acquisition ms method to physically detect pr8/34 (h1n1), x31 (h3n2), and victoria/75 (h3n2) epitopes bound to hla-a*02:01 on human epithelial cells follo ...201525646416
molecular epidemiology of influenza a virus infection among hospitalized children in vietnam during post-pandemic period.genetic variability makes influenza virus to escape the immunity and causes yearly epidemics. monitoring those changes is necessary for vaccine selection. in addition, h3n2 viruses were considered to be seeded from southeast asia before spreading globally. this study described the molecular epidemiology of influenza a during the post-pandemic season 2010-2011 in vietnam. nasopharyngeal samples were collected from children with respiratory infections at children's hospital 2, ho chi minh city. th ...201525648607
distribution of antibodies against influenza virus in pigs from farrow-to-finish farms in minas gerais state, brazil.swine influenza virus (siv) is the cause of an acute respiratory disease that affects swine worldwide. in brazil, siv has been identified in pigs since 1978. after the emergence of pandemic h1n1 in 2009 (h1n1pdm09), few studies reported the presence of influenza virus in brazilian herds.201525648743
protection against h5n1 by multiple immunizations with seasonal influenza vaccine in mice is correlated with h5 cross-reactive antibodies.current seasonal influenza vaccines are believed to confer protection against a narrow range of virus strains. however, their protective ability is commonly estimated based on an in vitro correlate of protection that only considers a subset of anti-influenza antibodies that are typically strain specific, i.e., hemagglutination inhibiting antibodies. here, we evaluate the breadth of protection induced with a seasonal trivalent influenza vaccine (composition h1n1 a/california/07/09, h3n2 a/victori ...201525659276
clinical experience with intravenous zanamivir under an emergency ind program in the united states (2011-2014).since the emergence of 2009 h1n1 virus, intravenous (iv) zanamivir has been authorized as an investigational treatment for patients with serious and life-threatening influenza through an emergency investigational new drug application (eind). this review encompasses the fda's eind database from may 2011 to june 2014.201525667992
a(h7n9) virus results in early induction of proinflammatory cytokine responses in both human lung epithelial and endothelial cells and shows increased human adaptation compared with avian h5n1 virus.similar to h5n1 viruses, a(h7n9) influenza viruses have been associated with severe respiratory disease and fatal outcomes in humans. while high viral load, hypercytokinemia, and pulmonary endothelial cell involvement are known to be hallmarks of h5n1 virus infection, the pathogenic mechanism of the a(h7n9) virus in humans is largely unknown. in this study, we assessed the ability of a(h7n9) virus to infect, replicate, and elicit innate immune responses in both human bronchial epithelial cells a ...201525673714
a mutant h3n2 influenza virus uses an alternative activation mechanism in tmprss2 knockout mice by loss of an oligosaccharide in the hemagglutinin stalk region.the host protease tmprss2 plays an essential role in proteolytic activation of the influenza a virus (iav) hemagglutinin (ha) protein possessing a monobasic cleavage site. however, after passages in tmprss2 knockout mice, an h3n2 subtype iav began to undergo cleavage activation of ha, showing high virulence in the mice due to the loss of an oligosaccharide at position 8 in the ha stalk region. thus, the h3n2 iav acquired cleavability by an alternative ha activation mechanism/protease(s).201525673722
molecular epidemiology and evolution of influenza a and b viruses during winter 2013-2014 in beijing, china.in this study, we investigated the molecular epidemiology and evolution of influenza viruses from patients infected during the 2013-2014 influenza season in beijing. a phylogenetic analysis of the hemagglutinin (ha) and neuraminidase (na) sequences of influenza a and b viruses from 18 patients (6 a(h1n1)pdm09, 4 h3n2, and 8 influenza b virus) was performed. among the influenza a viruses, a(h1n1)pdm09 was the dominant subtype, whereas the b/yamagata lineage was predominant for influenza b. the in ...201525676826
expression of h3n2 nucleoprotein in maize seeds and immunogenicity in mice.oral administration of maize-expressed h3n2 nucleoprotein induced antibody responses in mice showing the immunogenicity of plant-derived antigen and its potential to be utilized as a universal flu vaccine. influenza a viruses cause influenza epidemics that are devastating to humans and livestock. the vaccine for influenza needs to be reformulated every year to match the circulating strains due to virus mutation. influenza virus nucleoprotein (np) is a multifunctional rna-binding protein that is ...201525677970
ha1-specific indirect elisa for serological detection of canine influenza virus h3n2 infection in dogs.an indirect elisa using recombinant ha1 protein of canine influenza virus (civ) as a coating antigen was developed and characterized for its application to serosurveillance in dogs. the civ h3n2-specific indirect elisa was developed using recombinant ha1 protein (baculovirus-expression system) as a coating antigen. a total of 65 civ h3n2-positive or negative canine sera were tested by the indirect elisa for receiver operating characteristic (roc) analysis and results compared to those generated ...201525682751
heterosubtypic protection conferred by the human monoclonal antibody pn-sia28 against influenza a virus lethal infections in mice.pn-sia28 is a human monoclonal antibody (hu-mab) targeting highly conserved epitopes within the stem portion of the influenza virus hemagglutinin (ha) (n. clementi, et al, plos one 6:e28001, 2011, http://dx.doi.org/10.1371/journal.pone.0028001). previous in vitro studies demonstrated pn-sia28 neutralizing activities against phylogenetically divergent influenza a subtypes. in this study, the protective activity of pn-sia28 was evaluated in mice inoculated with lethal influenza a/wsn/33 (h1n1), a/ ...201525691648
challenges in antigenic characterization of circulating influenza a(h3n2) viruses during the 2011-2012 influenza season: an ongoing problem?genetic and antigenic characterization of 37 representative influenza a(h3n2) virus strains isolated in greece during the 2011-2012 winter season was performed to evaluate matching of the viruses with the seasonal influenza vaccine strain a/perth/16/2009. hemagglutinin gene sequence analysis revealed that all greek strains clustered within the victoria/208 genetic clade. furthermore, substitutions in the antigenic and glycosylation sites suggested potential antigenic drift. our hemagglutination ...201525694524
characterization of co-circulating swine influenza a viruses in north america and the identification of a novel h1 genetic clade with antigenic significance.multiple genetically and antigenically distinct hemagglutinin genes of the h1 and h3 influenza a virus (iav) subtypes co-circulate in north american swine. this diversity has evolved by repeated transmission of iavs from humans to swine and subsequent antigenic drift in swine. to understand the evolutionary dynamics of these diverse ha lineages in north american swine, we undertook a phylogenetic analysis of 1576 h1 and 607 h3 ha gene segments, as well as 834 n1 and 1293 n2 na gene segments, and ...201525701742
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
analysis of potential changes in seriousness of influenza a and b viruses in hong kong from 2001 to 2011.continued monitoring of the seriousness of influenza viruses is a public health priority. we applied time-series regression models to data on cardio-respiratory mortality rates in hong kong from 2001 to 2011. we used surveillance data on outpatient consultations for influenza-like illness, and laboratory detections of influenza types/subtypes to construct proxy measures of influenza activity. in the model we allowed the regression coefficients for influenza to drift over time, and adjusted for t ...201525703399
development and characterization of a panel of cross-reactive monoclonal antibodies generated using h1n1 influenza virus.to characterize the antigenic epitopes of the hemagglutinin (ha) protein of h1n1 influenza virus, a panel consisting of 84 clones of murine monoclonal antibodies (mabs) were generated using the ha proteins from the 2009 pandemic h1n1 vaccine lysate and the seasonal influenza h1n1(a1) vaccines. thirty-three (39%) of the 84 mabs were found to be strain-specific, and 6 (7%) of the 84 mabs were subtype-specific. twenty (24%) of the 84 mabs recognized the common ha epitopes shared by 2009 pandemic h1 ...201525708705
optimization of an enzyme-linked lectin assay suitable for rapid antigenic characterization of the neuraminidase of human influenza a(h3n2) viruses.antibodies to neuraminidase (na), the second most abundant surface protein of the influenza virus, contribute to protection against influenza virus infection. although traditional and miniaturized thiobarbituric acid (tba) neuraminidase inhibition (ni) assays have been successfully used to characterize the antigenic properties of na, these methods are cumbersome and not easily amendable to rapid screening. an additional difficulty of the ni assay is the interference by hemagglutinin (ha)-specifi ...201525712563
positive selection drives preferred segment combinations during influenza virus reassortment.influenza a virus (iav) has a segmented genome that allows for the exchange of genome segments between different strains. this reassortment accelerates evolution by breaking linkage, helping iav cross species barriers to potentially create highly virulent strains. challenges associated with monitoring the process of reassortment in molecular detail have limited our understanding of its evolutionary implications. we applied a novel deep sequencing approach with quantitative analysis to assess the ...201525713211
preparation of monopegylated cyanovirin-n's derivative and its anti-influenza a virus bioactivity in vitro and in vivo.influenza a virus (iav) has been raising public health and safety concerns worldwide. cyanovirin-n (cvn) is a prominent anti-iav candidate, but both cytotoxicity and immunogenicity have hindered the development of this protein as a viable therapy. in this article, linker-cvn (lcvn) with a flexible and hydrophilic polypeptide at the n-terminus was efficiently produced from the cytoplasm of escherichia coli at a >15-l scale. pegylation at the n-terminal α-amine of lcvn was also reformed as 20 kda ...201525713409
cross-reactivity of immunoglobulin a secreted on the nasal mucosa in mice nasally inoculated with inactivated h1n1 influenza a viruses in the presence of d-octaarginine-linked polymers.we evaluated cross-reactivity of immunoglobulin a (iga) secreted on the nasal mucosa in mice that were nasally inoculated 4 times with a mixture of inactivated h1n1 influenza a viruses and poly(n-vinylacetamide-co-acrylic acid) (pnva-co-aa) bearing d-octaarginine at 7-day intervals. three viral strains (a/puerto rico/8/34, a/new caledonia/20/99 ivr116, and a/solomon islands/03/2006) and d-octaarginine-linked polymers with different molecular weights were used as antigens and their carriers, resp ...201525720816
global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2013-2014.four world health organization (who) collaborating centres for reference and research on influenza and one who collaborating centre for the surveillance, epidemiology and control of influenza (who ccs) tested 10,641 viruses collected by who-recognized national influenza centres between may 2013 and may 2014 to determine 50% inhibitory concentration (ic50) data for neuraminidase inhibitors (nais) oseltamivir, zanamivir, peramivir and laninamivir. in addition, neuraminidase (na) sequence data, ava ...201525721488
comparison of the performance of 2 commercial multiplex pcr platforms for detection of respiratory viruses in upper and lower tract respiratory specimens.the performance of the clart® pneumovir system with that of the luminex xtag rvp fast v1 assay for detection of most common respiratory viruses in upper and lower tract respiratory specimens (n=183) from unique patients with influenza-like syndrome or lower tract respiratory infection. nested pcr coupled to automated sequencing was used for resolution of discrepancies. fully concordant results were obtained for a total of 122 specimens, whereas 56 specimens gave partially (n=21) or fully discord ...201525724853
estimating the life course of influenza a(h3n2) antibody responses from cross-sectional data.the immunity of a host population against specific influenza a strains can influence a number of important biological processes, from the emergence of new virus strains to the effectiveness of vaccination programmes. however, the development of an individual's long-lived antibody response to influenza a over the course of a lifetime remains poorly understood. accurately describing this immunological process requires a fundamental understanding of how the mechanisms of boosting and cross-reactivi ...201525734701
origins and evolutionary dynamics of h3n2 canine influenza virus.influenza a viruses (iavs) are maintained mainly in wild birds, and despite frequent spillover infections of avian iavs into mammals, only a small number of viruses have become established in mammalian hosts. a new h3n2 canine influenza virus (civ) of avian origin emerged in asia in the mid-2000s and is now circulating in dog populations of china and south korea, and possibly in thailand. the emergence of civ provides new opportunities for zoonotic infections and interspecies transmission. we ex ...201525740996
whole-genome sequences of influenza a(h3n2) viruses isolated from brazilian patients with mild illness during the 2014 season.the influenza a(h3n2) virus has circulated worldwide for almost five decades and is the dominant subtype in most seasonal influenza epidemics, as occurred in the 2014 season in south america. in this study we evaluate five whole genome sequences of influenza a(h3n2) viruses detected in patients with mild illness collected from january-march 2014. to sequence the genomes, a new generation sequencing (ngs) protocol was performed using the ion torrent pgm platform. in addition to analysing the comm ...201525742277
safety and immunogenicity of influenza whole inactivated virus vaccines: a phase i randomized clinical trial.influenza vaccine production capacity is still insufficient to meet global demand in case of a pandemic. to expand worldwide influenza vaccine production capacity, a solid and transferable egg-based influenza vaccine production process was established that is suitable for upscaling and technology transfer to vaccine manufacturers in low- and middle-income countries. as a proof-of-concept, the safety and immunogenicity of a pandemic whole inactivated virus (wiv) vaccine (h5n1) and a monovalent se ...201525751506
sparse serological evidence of h5n1 avian influenza virus infections in domestic cats, northeastern china.today the cross-species transmission of avian influenza viruses (aiv) are a great concern. a number of aiv strains are now enzootic among poultry, with h9n2 and highly pathogenic h5n1 aiv strains prevalent in china. h5n1 strains have been recognized to infect zoo and domestic feline species. in this serological study we sought to examine evidence that h5n1 strains have infected domestic cats in northeastern china. in 2013, we conducted a cross-sectional serological study of 916 healthy cats in h ...201525752867
population susceptibility to a variant swine-origin influenza virus a(h3n2) in vietnam, 2011-2012.a reassortant swine-origin a(h3n2) virus (a/swine/binhduong/03-9/2010) was detected through swine surveillance programmes in southern vietnam in 2010. this virus contains haemagglutinin and neuraminidase genes from a human a(h3n2) virus circulating around 2004-2006, and the internal genes from triple-reassortant swine influenza a viruses (iavs). to assess population susceptibility to this virus we measured haemagglutination inhibiting (hi) titres to a/swine/binhduong/03-9/2010 and to seasonal a/ ...201525761949
swine influenza virus pa and neuraminidase gene reassortment into human h1n1 influenza virus is associated with an altered pathogenic phenotype linked to increased mip-2 expression.swine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. in this study, the influenza virus reassortment rate in swine and human cells was determined. coinfection of swine cells with 2009 pandemic h1n1 virus (huh1n1) and an endemic swine h1n2 (a/swine/illinois/02860/09) virus (swh1n2) resulted in a 23% reassortment rate that was independent of α2,3- or α2,6-sialic acid distribution on the cells ...201525762737
[excess mortality associated with influenza in spain in winter 2012].an excess of mortality was detected in spain in february and march 2012 by the spanish daily mortality surveillance system and the «european monitoring of excess mortality for public health action» program. the objective of this article was to determine whether this excess could be attributed to influenza in this period.201725770916
antibody responses to influenza viruses in paediatric patients and their contacts at the onset of the 2009 pandemic in mexico.on april 2009, the mexican ministry of health received notification of cases of severe pneumonia mostly affecting young healthy people; this was the beginning of the first influenza pandemic of the 21st century. the nature of the immune response to the influenza a(h1n1)2009 pandemic strain in mexico at the beginning of the pandemic outbreak has not been completely defined. we describe the serological response to the 2009 pandemic influenza virus in paediatric patients with influenza-like illness ...201525771463
integrated sentinel surveillance linking genetic, antigenic, and epidemiologic monitoring of influenza vaccine-virus relatedness and effectiveness during the 2013-2014 influenza season.canada's sentinel physician surveillance network links genetic, antigenic, and vaccine effectiveness (ve) measures in an integrated platform of influenza monitoring, described here for the 2013-2014 influenza season of resurgent a(h1n1)pdm09 and late-season type b activity.201525784728
evaluation of the activity of influenza and influenza-like viruses in the epidemic season 2013/2014.infections caused by respiratory viruses can have different clinical symptoms, while specific set of symptoms can be induced by different viruses. despite usually mild course of disease, some viruses causing certain disease entity can result in serious complications. therefore, quick and appropriate diagnostic is crucial for administering proper treatment. in the epidemic season 2013/2014, 2,497 specimens were tested. infections caused by influenza viruses were confirmed in 9.8%, while infection ...201525786402
with flu numbers among staff increasing, hospitals report challenges, need for vigilance.with a flu vaccine that is largely missing the mark, eds around the country have their hands full with patients complaining of flu-like symptoms. the flu arrived earlier this year than usual, and by mid-january, it was still not clear whether the virus had peaked. many eds are struggling with staffing challenges as more personnel than usual are missing work because they have come down with the flu themselves. as a result, hospital administrators are stepping up infection control practices and ur ...201525793248
characteristics of influenza ha-na interdependence determined through a graphical technique.influenza viruses are characterized by two surface proteins - the hemagglutinin (ha) of which there are 16 varieties, and the neuraminidase (na) of which there are 9, each subtype characterized by its antigenic properties. although theoretically 16 x 9 combinations are possible, only a few like the h1n1, h3n2, etc are seen to occur more frequently. numerous studies with select subtypes like h1n1, h5n1, etc., have explained this phenomena by indicating that viral viability necessitates functional ...201425794303
analysis of cytokine production in a newly developed canine tracheal epithelial cell line infected with h3n2 canine influenza virus.the madin-darby canine kidney (mdck) cell line is typically used to analyze pathological features after canine influenza virus (civ) infection. however, mdck cells are not the ideal cell type, because they are kidney epithelial cells. therefore, we generated an immortalized canine tracheal epithelial cell line, ku-cbe, to more reliably study immune responses to civ infection in the respiratory tract. ku-cbe cells expressed the influenza virus receptor, α-2,3-sialic acid (sa), but not α-2,6-sa. k ...201525797195
protection against multiple influenza a virus strains induced by candidate recombinant vaccine based on heterologous m2e peptides linked to flagellin.matrix 2 protein ectodomain (m2e) is considered a promising candidate for a broadly protective influenza vaccine. m2e-based vaccines against human influenza a provide only partial protection against avian influenza viruses because of differences in the m2e sequences. in this work, we evaluated the possibility of obtaining equal protection and immune response by using recombinant protein on the basis of flagellin as a carrier of the m2e peptides of human and avian influenza a viruses. recombinant ...201525799221
mitochondrial antiviral signaling adaptor mediated apoptosis in h3n2 swine influenza virus infection is inhibited by viral protein ns1 in vitro.we investigated the in vitro role of mitochondrial antiviral signaling adaptor (mavs) in apoptosis induced by h3n2 swine influenza virus infection and the influence of viral ns1 (nonstructural protein 1) protein on this process. h3n2 swine influenza virus (siv, a/swine/shandong/3/2005) was co-cultured with human lung epithelial a549 cells. the relationship of mavs expression to siv replication and apoptosis, and the influence of viral proteins on mavs functions were studied. the data indicate th ...201525800220
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