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detection of low pathogenic avian influenza viruses in wild birds in castilla-la mancha (south central spain).the iberian peninsula is located along the east atlantic and black sea/mediterranean flyways and is the third ranking european country as wintering quarter for wild migrating birds after turkey and rumania. for these reasons, spanish wetlands are of importance in aiv surveillance, and of great interest for the study of the epidemiology of lpaiv under mediterranean climate conditions. nevertheless, information on prevalence of lpaiv viruses in spain is still scarce and is restricted to two serolo ...201020605691
pathogenesis and transmissibility of highly (h7n1) and low (h7n9) pathogenic avian influenza virus infection in red-legged partridge (alectoris rufa).abstract: an experimental infection with highly pathogenic avian influenza virus (hpaiv) and low pathogenic avian influenza virus (lpaiv) was carried out in red-legged partridges (alectoris rufa) in order to study clinical signs, gross and microscopic lesions, and viral distribution in tissues and viral shedding. birds were infected with a hpaiv subtype h7n1 (a/chicken/italy/5093/1999) and a lpaiv subtype h7n9 (a/anas crecca/spain/1460/2008). uninoculated birds were included as contacts in both ...201121314907
avian influenza in north america, 2009-2011.all reports of avian influenza virus infections in poultry and isolations from wild bird species in canada, the united states, and mexico between 2009 and 2011 involved low pathogenic avian influenza. all three countries reported outbreaks of low pathogenic notifiable avian influenza in poultry during this period. the reports involved outbreaks of h5n2 among commercial turkeys in canada in 2009 and 2010; outbreaks of h5n3 in turkeys in 2009, h5n2 in chickens in 2010, h7n3 in turkeys in 2011, and ...201223402102
an analysis of microbiota-targeted therapies in patients with avian influenza virus subtype h7n9 infection.selective prophylactic decontamination of the digestive tract is a strategy for the prevention of secondary nosocomial infection in patients with avian influenza virus subtype h7n9 infection. our aim was to summarize the effectiveness of these therapies in re-establishing a stable and diverse microbial community, and reducing secondary infections.201424990477
histopathological findings in a critically ill patient with avian influenza a (h7n9).to date, data regarding the pulmonary histopathology of human h7n9 disease are scarce. we herein describe a patient with a severe case of avian influenza a (h7n9). a chest computerized tomography (ct) scan showed diffuse ground-glass opacities and consolidation throughout the lungs. a resection of pulmonary bullae in the right middle lobe was performed by video-assisted thoracic surgery (vats) based on the extracorporeal membrane oxygenation (ecmo) supportive technique on the 23(rd) day after th ...201526793388
efficacy of oseltamivir-peramivir combination therapy compared to oseltamivir monotherapy for influenza a (h7n9) infection: a retrospective study.since the novel h7n9 avian influenza outbreak occurred in china in 2013, neuraminidase inhibitors (nais) such as oseltamivir and peramivir have been used as first-line drugs to treat the influenza virus infection. this study aimed to compare the efficacy of oseltamivir-peramivir combination therapy versus oseltamivir monotherapy.201526864456
implementing hospital-based surveillance for severe acute respiratory infections caused by influenza and other respiratory pathogens in new zealand.recent experience with pandemic influenza a(h1n1)pdm09 highlighted the importance of global surveillance for severe respiratory disease to support pandemic preparedness and seasonal influenza control. improved surveillance in the southern hemisphere is needed to provide critical data on influenza epidemiology, disease burden, circulating strains and effectiveness of influenza prevention and control measures. hospital-based surveillance for severe acute respiratory infection (sari) cases was esta ...201425077034
clinical evaluation of the new high-throughput luminex nxtag respiratory pathogen panel assay for multiplex respiratory pathogen detection.a broad range of viral and bacterial pathogens can cause acute respiratory tract infection. for rapid detection of a broad respiratory pathogen spectrum, multiplex real-time pcr is ideal. this study evaluated the performance of the new luminex nxtag respiratory pathogen panel (nxtag-rpp) in comparison with the biofire filmarray respiratory panel (fa-rp) or singleplex real-time pcr as reference. a total of 284 clinical respiratory specimens and 3 influenza a/h7n9 viral culture samples were tested ...201627122380
favipiravir (t-705), a novel viral rna polymerase inhibitor.favipiravir (t-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an antiviral drug that selectively inhibits the rna-dependent rna polymerase of influenza virus. it is phosphoribosylated by cellular enzymes to its active form, favipiravir-ribofuranosyl-5'-triphosphate (rtp). its antiviral effect is attenuated by the addition of purine nucleic acids, indicating the viral rna polymerase mistakenly recognizes favipiravir-rtp as a purine nucleotide. favipiravir is active against a broad range of inf ...201324084488
transcriptomic characterization of the novel avian-origin influenza a (h7n9) virus: specific host response and responses intermediate between avian (h5n1 and h7n7) and human (h3n2) viruses and implications for treatment options.a novel avian-origin h7n9 influenza a virus (iav) emerged in china in 2013, causing mild to lethal human respiratory infections. h7n9 originated with multiple reassortment events between avian viruses and carries genetic markers of human adaptation. determining whether h7n9 induces a host response closer to that with human or avian iav is important in order to better characterize this emerging virus. here we compared the human lung epithelial cell response to infection with a/anhui/01/13 (h7n9) ...201424496798
influenza a viruses from wild birds in guatemala belong to the north american lineage.the role wild bird species play in the transmission and ecology of avian influenza virus (aiv) is well established; however, there are significant gaps in our understanding of the worldwide distribution of these viruses, specifically about the prevalence and/or significance of aiv in central and south america. as part of an assessment of the ecology of aiv in guatemala, we conducted active surveillance in wild birds on the pacific and atlantic coasts. cloacal and tracheal swab samples taken from ...201222427902
a novel approach for preparation of the antisera reagent for potency determination of inactivated h7n9 influenza vaccines.the potency of inactivated influenza vaccines is determined using a single-radial immunodiffusion (srid) assay and requires standardized reagents consisting of a reference antigen and an influenza strain-specific antiserum. timely availability of reagents is a critical step in influenza vaccine production, and the need for backup approaches for reagent preparation is an important component of pandemic preparedness.201626616263
novel avian-origin influenza a (h7n9) virus attachment to the respiratory tract of five animal models.we determined the pattern of attachment of the avian-origin h7n9 influenza viruses a/anhui/1/2013 and a/shanghai/1/2013 to the respiratory tract in ferrets, macaques, mice, pigs, and guinea pigs and compared it to that in humans. the h7n9 attachment pattern in macaques, mice, and to a lesser extent pigs and guinea pigs resembled that in humans more closely than the attachment pattern in ferrets. this information contributes to our knowledge of the different animal models for influenza.201424478425
evaluation of the human adaptation of influenza a/h7n9 virus in pb2 protein using human and swine respiratory tract explant cultures.novel avian h7n9 virus emerged in china in 2013 resulting in a case fatality rate of around 39% and continues to pose zoonotic and pandemic risk. amino acid substitutions in pb2 protein were shown to influence the pathogenicity and transmissibility of h7n9 following experimental infection of ferrets and mice. in this study, we evaluated the role of amino acid substitution pb2-627k or compensatory changes at pb2-591k and pb2-701n, on the tropism and replication competence of h7n9 viruses for huma ...201627739468
species difference in anp32a underlies influenza a virus polymerase host restriction.influenza pandemics occur unpredictably when zoonotic influenza viruses with novel antigenicity acquire the ability to transmit amongst humans. host range breaches are limited by incompatibilities between avian virus components and the human host. barriers include receptor preference, virion stability and poor activity of the avian virus rna-dependent rna polymerase in human cells. mutants of the heterotrimeric viral polymerase components, particularly pb2 protein, are selected during mammalian ...026738596
a case report demonstrating the utility of next generation sequencing in analyzing serial samples from the lung following an infection with influenza a (h7n9) virus.bacterial pneumonia is a well-recognized sequela of patient suffering from influenza, and a key factor, with cytokine dysregulation, that contribute to severe disease and mortality.201626826577
[a severe h7n9 bird flu virus patient complicated acinetobacter baumannii infection: a syndrome analysis of one case]. 201526591373
serial high-resolution analysis of blood virome and host cytokines expression profile of a patient with fatal h7n9 infection by massively parallel rna sequencing.bloodstream infections and cytokine dysregulation are associated with high rates of morbidity and mortality among patients with influenza virus h7n9 infection. here, massively parallel rna sequencing was used to serially analyse plasma viruses and cytokine transcriptomes of a fatal h7n9-related case at successive times throughout the clinical course of infection. the results showed that acute viraemia with h7n9 virus occurred, and the virus was sensitive to antiviral therapy with oseltamivir. in ...201525882353
ards associated with pneumonia caused by avian influenza a h7n9 virus treated with extracorporeal membrane oxygenation.this is a sporadic h7n9 avian influenza case that was the first severe imported case in beijing and the first case of hebei province in china. a 61-year-old female who had rapidly progressive pneumonia with respiratory distress and bilateral exduation and consolidation changes on chest x-ray and computerized tomography (ct) scan that did not respond to ordinary antibiotics was diagnosed with influenza a (h7n9) infection in our hospital on july 19, 2013. intravenous peramivir, veno-venous extraco ...201524725670
preparation of quadri-subtype influenza virus-like particles using bovine immunodeficiency virus gag protein.influenza vlps comprised of hemagglutinin (ha), neuraminidase (na), and matrix (m1) proteins have been previously used for immunological and virological studies. here we demonstrated that influenza vlps can be made in sf9 cells by using the bovine immunodeficiency virus gag (bgag) protein in place of m1. we showed that bgag can be used to prepare vlps for several influenza subtypes including h1n1 and h10n8. furthermore, by using bgag, we prepared quadri-subtype vlps, which co-expressed within th ...201626529299
the effect of probiotic treatment on patients infected with the h7n9 influenza virus.a novel avian-origin influenza a (h7n9) virus emerged and spread among humans in eastern china in 2013. prophylactic treatment with antibiotics and probiotics for secondary infection is as important as antiviral treatment. this study aims to assess the ability of probiotic treatment to restore internal homeostasis under antibiotic pressure and to reduce/ameliorate the risk of secondary infections resulting from infection with the h7n9 virus.201626987119
computational approach for predicting the conserved b-cell epitopes of hemagglutinin h7 subtype influenza virus.an avian-origin influenza h7n9 virus epidemic occurred in china in 2013-2014, in which >422 infected people suffered from pneumonia, respiratory distress syndrome and septic shock. h7n9 viruses belong to the h7 subtype of avian-origin influenza viruses (aiv-h7). hemagglutinin (ha) is a vital membrane protein of aiv that has an important role in host recognition and infection. the epitopes of ha are significant determinants of the regularity of epidemic and viral mutation and recombination mechan ...201627703505
new global viral threats.infectious diseases have caused great catastrophes in human history, as in the example of the plague, which wiped out half of the population in europe in the 14th century. ebola virus and h7n9 avian influenza virus are 2 lethal pathogens that we have encountered in the second decade of the 21st century. ebola infection is currently being seen in west africa, and h7n9 avian flu appears to have settled in southeast asia. this article focuses on the current situation and the future prospects of the ...201525828274
influence of h7n9 virus infection and associated treatment on human gut microbiota.between march and june, 2013, forty h7n9 patients were hospitalized in our hospital. next-generation sequencing technologies have been used to sequence the fecal dna samples of the patient, the within sample diversity analysis, enterotyping, functional gene and metagenomic species analysis have been carried on both the patients and healthy controls. the influence of associated treatment in h7n9 infected patients is dramatic and was firstly revealed in species level due to deep sequencing technol ...201526490635
equine and canine influenza h3n8 viruses show minimal biological differences despite phylogenetic divergence.the a/h3n8 canine influenza virus (civ) emerged from a/h3n8 equine influenza virus (eiv) around the year 2000 through the transfer of a single virus from horses to dogs. we defined and compared the biological properties of eiv and civ by examining their genetic variation, infection, and growth in different cell cultures, receptor specificity, hemagglutinin (ha) cleavage, and infection and growth in horse and dog tracheal explant cultures. comparison of sequences of viruses from horses and dogs r ...201525903329
influenza h7n9 lah-hbc virus-like particle vaccine with adjuvant protects mice against homologous and heterologous influenza viruses.the long alpha-helix (lah) region located in influenza virus hemagglutinin (ha) shows conservation among different influenza a strains, which could be used as a candidate target of influenza vaccines. moreover, the hepatitis b virus core protein (hbc) is a carrier for heterologous epitopes in eliciting effective immune responses. we inserted the lah region of h7n9 influenza virus into the hbc and prepared the lah-hbc protein, which were capable of self-assembly into virus-like particles (vlp), b ...201627866773
an avian influenza a (h7n9) virus vaccine candidate based on the fusion protein of hemagglutinin globular head and salmonella typhimurium flagellin.a novel influenza virus, subtype h7n9, circulated through china in 2013-2014. its higher rates of human infection in a wide range of locations within china and the associated increased likelihood of human-to-human transmission have caused global concern. recombinant subunit vaccines provide safe and targeted protection against viral infections. however, the protective efficacy of recombinant subunit vaccines tends to be less potent than vaccines made from whole viruses. studies have shown that b ...201526286143
recombinant influenza a virus hemagglutinin ha2 subunit protects mice against influenza a(h7n9) virus infection.a novel avian influenza a(h7n9) virus has emerged to infect humans in eastern china since 2013. an effective vaccine is needed because of the high mortality despite antiviral treatment and intensive care. we sought to develop an effective vaccine for a(h7n9) virus. the ha2 subunit was chosen as the vaccine antigen because it is highly conserved among the human a(h7n9) virus strains. moreover, in silico analysis predicted two immunogenic regions within the ha2 subunit that may contain potential h ...201525616843
h5 n-terminal β sheet promotes oligomerization of h7-ha1 that induces better antibody affinity maturation and enhanced protection against h7n7 and h7n9 viruses compared to inactivated influenza vaccine.initiation of mass vaccination is critical in response to influenza pandemic. there is an urgent need of a simple, rapid method for production of influenza vaccine that is more effective than current traditional influenza vaccines. recent h7n9 transmissions to humans in china with high morbidity/mortality initiated extensive vaccine evaluation. we produced the ha1 domains (amino acids 1-320) from h7n9 and h7n7 strains in e. coli. both were found to contain primarily monomers/trimers with low oli ...201425284811
protection against influenza h7n9 virus challenge with a recombinant np-m1-hsp60 protein vaccine construct in balb/c mice.a novel influenza virus of h7n9 subtype circulated throughout china in 2013. the high fatality rate, appearance of several family clusters, and transmission in animal models observed during this outbreak accelerated efforts to identify effective strategies to prevent the spread of this influenza subtype. in this study, the recombinant protein np-m1-hsp60, a fusion of the nucleoprotein and m1 matrix protein of the a/pr/8/34 (h1n1) influenza virus strain and hsp60, was effectively expressed in esc ...201425173575
high-yield soluble expression of recombinant influenza virus antigens from escherichia coli and their potential uses in diagnosis.although antiviral drugs and vaccines have been successful for mitigating influenza virus infections, the lack of general technical platform for the timely supply of soluble and highly purified influenza viral antigens presents a serious bottleneck for the subsequent analysis for the effective control of the viral disease. using the escherichia coli (e. coli) lysyl trna synthetase (lysrs) as a novel fusion partner, this study reports the soluble expression of influenza viral proteins in e. coli ...201424216235
genome sequence of a novel h10n9 avian influenza virus isolated from chickens in a live poultry market in eastern china.an h10n9 avian influenza virus (aiv) strain, a/chicken/jiangsu/rd5/2013, was isolated in china. the hemagglutinin (ha) and neuraminidase (na) genes in this strain originated from h10n1 and h7n9 aivs, respectively, and the other genes derived from h7n3 aivs. sequence analysis implies that the h10n9 aiv may be an na gene donor for the human h7n9 influenza viruses.201323814107
emergence in china of human disease due to avian influenza a(h10n8)--cause for concern?in december 2013, china reported the first human case of avian influenza a(h10n8). a 73-year-old female with chronic diseases who had visited a live poultry market succumbed with community-acquired pneumonia. while human infections with avian influenza viruses are usually associated with subtypes prevalent in poultries, a(h10n8) isolates were mostly found in migratory birds and only recently in poultries. although not possible to predict whether this single intrusion by a(h10n8) is an accident o ...201424406432
emergence and evolution of h10 subtype influenza viruses in poultry in china.the cases of human infections with h10n8 viruses identified in late 2013 and early 2014 in jiangxi, china, have raised concerns over the origin, prevalence, and development of these viruses in this region. our long-term influenza surveillance of poultry and migratory birds in southern china in the past 12 years showed that h10 influenza viruses have been introduced from migratory to domestic ducks over several winter seasons at sentinel duck farms at poyang lake, where domestic ducks share their ...201525589662
the avian influenza h9n2 at avian-human interface: a possible risk for the future pandemics.the avian influenza subtype h9n2 is considered a low pathogenic virus which is endemic in domestic poultry of a majority of asian countries. many reports of seropositivity in occupationally poultry-exposed workers and a number of confirmed human infections with an h9n2 subtype of avian influenza have been documented up to now. recently, the human infections with both h7n9 and h10n8 viruses highlighted that h9n2 has a great potential for taking a part in the emergence of new human-infecting virus ...201628083072
the complexity of human infected aiv h5n6 isolated from china.novel avian influenza viruses (aivs) of h7n9, h10n8, and h5n6 are currently circulating in china's poultry flocks, occasionally infecting human and other mammals. human infected aiv h5n6 in china during 2014-2015 is believed to be a triple reassortant originated from h6n6 and two clades of h5 viruses. the current report suggests that its reassortment history is more complicated.201627782815
pb2-q591k mutation determines the pathogenicity of avian h9n2 influenza viruses for mammalian species.influenza a subtype h9n2 is widespread and prevalent in poultry. it has repeatedly transmitted zoonotically to cause mild influenza-like illness in humans and is regarded as a potential pandemic candidate. in additon, the six internal genes of h7n9 and h10n8 viruses which caused infection in human in china as well as some of the highly pathogenic h5n1 strains are origined from h9n2. previous studies have shown that the mammalian adaptation pb2-q591k contributes to the pathogenicity of h5n1 and h ...201727684944
avian influenza a viruses: evolution and zoonotic infection.although efficient human-to-human transmission of avian influenza virus has yet to be seen, in the past two decades avian-to-human transmission of influenza a viruses has been reported. influenza a/h5n1, in particular, has repeatedly caused human infections associated with high mortality, and since 1998 the virus has evolved into many clades of variants with significant antigenic diversity. in 2013, three (a/h7n9, a/h6n1, and a/h10n8) novel avian influenza viruses (aivs) breached the animal-huma ...201627486732
the ecology and adaptive evolution of influenza a interspecies transmission.since 2013, there have been several alarming influenza-related events; the spread of highly pathogenic avian influenza h5 viruses into north america, the detection of h10n8 and h5n6 zoonotic infections, the ongoing h7n9 infections in china and the continued zoonosis of h5n1 viruses in parts of asia and the middle east. the risk of a new influenza pandemic increases with the repeated interspecies transmission events that facilitate reassortment between animal influenza strains; thus, it is of utm ...201727426214
prevailing pa mutation k356r in avian influenza h9n2 virus increases mammalian replication and pathogenicity.adaptation of the viral polymerase complex comprising pb1, pb2, and pa is necessary for efficient influenza a virus replication in new host species. we found that pa mutation k356r (pa-k356r) has become predominant since 2014 in avian h9n2 viruses in china as with seasonal human h1n1 viruses. the same mutation is also found in most human isolates of emergent avian h7n9 and h10n8 viruses whose six internal gene segments are derived from the h9n2 virus. we further demonstrated the mammalian adapti ...201627384648
prevalence and diversity of h9n2 avian influenza in chickens of northern vietnam, 2014.despite their classification as low pathogenicity avian influenza viruses (lpaiv), a/h9n2 viruses cause significant losses in poultry in many countries throughout asia, the middle east and north africa. to date, poultry surveillance in vietnam has focused on detection of influenza h5 viruses, and there is limited understanding of influenza h9 epidemiology and transmission dynamics. we determined prevalence and diversity of influenza a viruses in chickens from live bird markets (lbm) of 7 norther ...201627340015
[genomic characteristics of 2 strains of influenza a(h9n2)virus isolated from human infection cases in anhui province].to understand genomic characteristics of 2 strains of influenza a(h9n2)virus isolated from human infection cases in anhui province in 2015.201627188368
avian influenza virus in pregnancy.the unprecedented epizootic of avian influenza viruses, such as h5n1, h5n6, h7n1 and h10n8, has continued to cause disease in humans in recent years. in 2013, another novel influenza a (h7n9) virus emerged in china, and 30% of those patients died. pregnant women are particularly susceptible to avian influenza and are more likely to develop severe complications and to die, especially when infection occurs in the middle and late trimesters. viremia is believed to occur infrequently, and thus verti ...201627187752
phylogenetic analysis and pathogenicity assessment of two strains of avian influenza virus subtype h9n2 isolated from migratory birds: high homology of internal genes with human h10n8 virus.two human-infecting avian influenza viruses (aivs), h7n9 and h10n8, have emerged in china, which further indicate that the h9n2 subtype of aivs, as an internal gene donor, may have an important role in the generation of new viruses with cross-species transmissibility and pathogenicity. h9n2 viruses that contain such internal genes widely exist in poultry but are rarely reported in migratory birds. in this study, two strains of the h9n2 virus were isolated from fecal samples of migratory birds in ...201626973600
pb2-588 v promotes the mammalian adaptation of h10n8, h7n9 and h9n2 avian influenza viruses.human infections with avian influenza h7n9 or h10n8 viruses have been reported in china, raising concerns that they might cause human epidemics and pandemics. however, how these viruses adapt to mammalian hosts is unclear. here we show that besides the commonly recognized viral polymerase subunit pb2 residue 627 k, other residues including 87e, 292 v, 340 k, 588 v, 648 v, and 676 m in pb2 also play critical roles in mammalian adaptation of the h10n8 virus. the avian-origin h10n8, h7n9, and h9n2 ...201626782141
pb2 subunit of avian influenza virus subtype h9n2: a pandemic risk factor.avian influenza viruses of subtype h9n2 that are found worldwide are occasionally transmitted to humans and pigs. furthermore, by co-circulating with other influenza subtypes, they can generate new viruses with the potential to also cause zoonotic infections, as observed in 1997 with h5n1 or more recently with h7n9 and h10n8 viruses. comparative analysis of the adaptive mutations in polymerases of different viruses indicates that their impact on the phylogenetically related h9n2 and h7n9 polymer ...201626560088
hemagglutinin stalk- and neuraminidase-specific monoclonal antibodies protect against lethal h10n8 influenza virus infection in mice.between november 2013 and february 2014, china reported three human cases of h10n8 influenza virus infection in the jiangxi province, two of which were fatal. using hybridoma technology, we isolated a panel of h10- and n8-directed monoclonal antibodies (mabs) and further characterized the binding reactivity of these antibodies (via enzyme-linked immunosorbent assay) to a range of purified virus and recombinant protein substrates. the h10-directed mabs displayed functional hemagglutination inhibi ...201526512088
emerging influenza strains in the last two decades: a threat of a new pandemic?in the last 20 years, novel non-seasonal influenza viruses have emerged, most of which have originated from birds. despite their apparent inability to cause pandemics, with the exception of h1n1 swine influenza virus, these viruses still constitute a constant threat to public health. while general concern has decreased after the peak of the h5n1 virus, in recent years several novel reassorted influenza viruses (e.g., h7n9, h9n2, h10n8) have jumped the host-species barrier and are under surveilla ...201526344952
evolutionary dynamics and global diversity of influenza a virus.the increasing number of zoonotic infections caused by influenza a virus (iav) subtypes of avian origin (e.g., h5n1 and h7n9) in recent years underscores the need to better understand the factors driving iav evolution and diversity. to evaluate the current feasibility of global analyses to contribute to this aim, we evaluated information in the public domain to explore iav evolutionary dynamics, including nucleotide substitution rates and selection pressures, using 14 iav subtypes in 32 differen ...201526311890
challenges and strategies of laboratory diagnosis for newly emerging influenza viruses in taiwan: a decade after sars.since the first case of severe acute respiratory syndrome (sars) in taiwan was identified in march 2003, viral respiratory infections, in particular the influenza virus, have become a national public health concern. taiwan would face a serious threat of public health problems if another sars epidemic overlapped with a flu outbreak. after sars, the taiwan centers for disease control accelerated and strengthened domestic research on influenza and expanded the exchange of information with internati ...201526290876
epidemiology, evolution, and recent outbreaks of avian influenza virus in china.novel reassortants of h7n9, h10n8, and h5n6 avian influenza viruses (aivs) are currently circulating in china's poultry flocks, occasionally infecting humans and other mammals. combined with the sometimes enzootic h5n1 and h9n2 strains, this cauldron of genetically diverse aivs pose significant risks to public health. here, we review the epidemiology, evolution, and recent outbreaks of aivs in china, discuss reasons behind the recent increase in the emergence of novel aivs, and identify warning ...201526063419
genesis of avian influenza h9n2 in bangladesh.avian influenza subtype h9n2 is endemic in many bird species in asia and the middle east and has contributed to the genesis of h5n1, h7n9 and h10n8, which are potential pandemic threats. h9n2 viruses that have spread to bangladesh have acquired multiple gene segments from highly pathogenic (hp) h7n3 viruses that are presumably in pakistan and currently cocirculate with hp h5n1. however, the source and geographic origin of these h9n2 viruses are not clear. we characterized the complete genetic se ...201426038507
human infection with an avian influenza a (h9n2) virus in the middle region of china.during the epidemic period of the novel h7n9 viruses, an influenza a (h9n2) virus was isolated from a 7-year-old boy with influenza-like illness in yongzhou city of hunan province in november 2013. to identify the possible source of infection, environmental specimens collected from local live poultry markets epidemiologically linked to the human case in yongzhou city were tested for influenza type a and its subtypes h5, h7, and h9 using real-time rt-pcr methods as well as virus isolation, and fo ...201525965534
beagle dogs have low susceptibility to bj94-like h9n2 avian influenza virus.in china, dogs are considered significant intermediate hosts of influenza viruses and have been reported to be infected with h9n2; additionally, a reassortant h9n2 virus has been isolated in dogs. currently, there are three different lineages of h9n2, including bj94-like, g1-like, and y439-like lineages; bj94-like h9n2 has been circulating in various types of poultry in southern china. additionally, a number of studies have reported that h9n2 evolves rapidly and is frequently reassorted with h5n ...201525675837
structure and receptor binding preferences of recombinant hemagglutinins from avian and human h6 and h10 influenza a virus subtypes.during 2013, three new avian influenza a virus subtypes, a(h7n9), a(h6n1), and a(h10n8), resulted in human infections. while the a(h7n9) virus resulted in a significant epidemic in china across 19 provinces and municipalities, both a(h6n1) and a(h10n8) viruses resulted in only a few human infections. this study focuses on the major surface glycoprotein hemagglutinins from both of these novel human viruses. the detailed structural and glycan microarray analyses presented here highlight the idea t ...201525673707
identification of potential virulence determinants associated h9n2 avian influenza virus pb2 e627k mutation by comparative proteomics.some highly pathogenic h5n1, h7n9, and h10n8 isolated from china carried six internal genes from h9n2 avian influenza viruses (aiv) and the key amino acids at 627 in pb2 of these viruses had mutated to k. to investigate the mechanism of increased pathogenicity for h9n2 aiv pb2 627k, we analyzed the difference in mouse lung proteins expression response to pb2 k627e. by itraq method, we found that the mutated k627e contributed to a set of differentially expressed lung proteins, including five upre ...201525641917
muscovy duck retinoic acid-induced gene i (mdrig-i) functions in innate immunity against h9n2 avian influenza viruses (aiv) infections.retinoic acid inducible gene i (rig-i) is a cytosolic pattern recognition receptor that senses pathogen-associated molecular patterns (pamps). muscovy duck (cairina moschata) is a large duck different from other species of ducks, and is more susceptible to some microbial pathogens. in this study, the muscovy duck rig-i gene (mdrig-i) was identified. quantitative rt-pcr showed that mdrig-i mrna was widely expressed in different tissues, especially in those with mucosa. rig-i null df-1 cells trans ...201525604129
genetic diversity of avian influenza a (h10n8) virus in live poultry markets and its association with human infections in china.following the first human infection with the influenza a (h10n8) virus in nanchang, china in december 2013, we identified two additional patients on january 19 and february 9, 2014. the epidemiologic, clinical, and virological data from the patients and the environmental specimen collected from 23 local live poultry markets (lpms) were analyzed. the three h10n8 cases had a history of poultry exposure and presented with high fever (>38°c), rapidly progressive pneumonia and lymphopenia. substantia ...201525591167
structural basis for preferential avian receptor binding by the human-infecting h10n8 avian influenza virus.since december 2013, at least three cases of human infections with h10n8 avian influenza virus have been reported in china, two of them being fatal. to investigate the epidemic potential of h10n8 viruses, we examined the receptor binding property of the first human isolate, a/jiangxi-donghu/346/2013 (jd-h10n8), and determined the structures of its haemagglutinin (ha) in complex with both avian and human receptor analogues. our results suggest that jd-h10n8 preferentially binds the avian receptor ...201525574798
phylogeography of avian influenza a h9n2 in china.during the past two decades, avian influenza a h9n2 viruses have spread geographically and ecologically in china. other than its current role in causing outbreaks in poultry and sporadic human infections by direct transmission, h9n2 virus could also serve as an progenitor for novel human avian influenza viruses including h5n1, h7n9 and h10n8. hence, h9n2 virus is becoming a notable threat to public health. however, despite multiple lineages and genotypes that were detected by previous studies, t ...201425511561
enzootic genotype s of h9n2 avian influenza viruses donates internal genes to emerging zoonotic influenza viruses in china.avian influenza viruses of subtype h9n2 are widely prevalent in poultry in many asian countries, and the segmented nature of the viral genome results in multiple distinct genotypes via reassortment. in this study, genetic evolution of h9n2 viruses circulating in eastern china during 2007-2013 was analyzed. the results showed that the diversity of the gene constellations generated six distinct genotypes, in which a novel genotype (s) bearing the backbone of a/chicken/shanghai/f/98-like viruses by ...201425457363
h9n2 influenza virus in china: a cause of concern.the recent human infection with avian influenza virus revealed that h9n2 influenza virus is the gene donor for h7n9 and h10n8 viruses infecting humans. the crucial role of h9n2 viruses at the animal-human interface might be due to the wide host range, adaptation in both poultry and mammalian, and extensive gene reassortment. as the most prevalent subtype of influenza viruses in chickens in china, h9n2 also causes a great economic loss for the poultry industry, even under the long-term vaccinatio ...201525384439
antibodies against h10n8 avian influenza virus among animal workers in guangdong province before november 30, 2013, when the first human h10n8 case was recognized.considered an epicenter of pandemic influenza virus generation, southern china has recently seen an increasing number of human h7n9 infections. however, it is not the only threat. on 30 november 2013, a human h10n8 infection case was first described in china. the origin and genetic diversity of this novel virus is similar to that of h7n9 virus. as h10n8 avian influenza virus (aiv) was first identified from a duck in guangdong province during 2012 and there is also evidence of h10n8 infected dogs ...201425348464
investigation of avian influenza virus in poultry and wild birds due to novel avian-origin influenza a(h10n8) in nanchang city, china.multiple reassortment events within poultry and wild birds had resulted in the establishment of another novel avian influenza a(h10n8) virus, and finally resulted in human death in nanchang, china. however, there was a paucity of information on the prevalence of avian influenza virus in poultry and wild birds in nanchang area. we investigated avian influenza virus in poultry and wild birds from live poultry markets, poultry countyards, delivery vehicles, and wild-bird habitats in nanchang. we an ...201525284683
surveillance for emerging respiratory viruses.several new viral respiratory tract infectious diseases with epidemic potential that threaten global health security have emerged in the past 15 years. in 2003, who issued a worldwide alert for an unknown emerging illness, later named severe acute respiratory syndrome (sars). the disease caused by a novel coronavirus (sars-cov) rapidly spread worldwide, causing more than 8000 cases and 800 deaths in more than 30 countries with a substantial economic impact. since then, we have witnessed the emer ...201425189347
zoonotic infections with avian influenza a viruses and vaccine preparedness: a game of "mix and match".various direct avian-to-human transmissions of influenza a virus subtypes upon exposure to infected poultry have been previously observed in the past decades. although some of these strains caused lethal infections, the lack of sustained person-to-person transmission has been the major factor that prevented these viruses from causing new pandemics. in 2013, three (a/h7n9, a/h6n1, and a/h10n8) novel avian influenza viruses (aivs) yet again breached the animal-human host species barrier in asia. n ...201425003087
receptor binding by h10 influenza viruses.h10n8 follows h7n9 and h5n1 as the latest in a line of avian influenza viruses that cause serious disease in humans and have become a threat to public health. since december 2013, three human cases of h10n8 infection have been reported, two of whom are known to have died. to gather evidence relating to the epidemic potential of h10 we have determined the structure of the haemagglutinin of a previously isolated avian h10 virus and we present here results relating especially to its receptor-bindin ...201424870229
[a report of first fatal case of h10n8 avian influenza virus pneumonia in the world].to report the treatment process of the first case of human pneumonia resulted from h10n8 avian influenza virus infection in the world for providing the data for clinical diagnosis and treatment.201424524404
clinical and epidemiological characteristics of a fatal case of avian influenza a h10n8 virus infection: a descriptive study.human infections with different avian influenza viruses--eg, h5n1, h9n2, and h7n9--have raised concerns about pandemic potential worldwide. we report the first human infection with a novel reassortant avian influenza a h10n8 virus.201424507376
a new piece in the puzzle of the novel avian-origin influenza a (h7n9) virus.using phylogenetic analysis on newly available sequences, we characterize a/chicken/jiangsu/rd5/2013(h10n9) as currently closest precursor strain for the na segment in the novel avian-origin h7n9 virus responsible for an outbreak in china. we also show that the internal segments of this precursor strain are closely related to those of the presumed precursor for the ha segment, a/duck/zhejiang/12/2011(h7n3), which indicates that the sources of both ha and na donors for the reassortant virus are o ...201324160334
genetically diverse low pathogenicity avian influenza a virus subtypes co-circulate among poultry in bangladesh.influenza virus surveillance, poultry outbreak investigations and genomic sequencing were assessed to understand the ecology and evolution of low pathogenicity avian influenza (lpai) a viruses in bangladesh from 2007 to 2013. we analyzed 506 avian specimens collected from poultry in live bird markets and backyard flocks to identify influenza a viruses. virus isolation-positive specimens (n = 50) were subtyped and their coding-complete genomes were sequenced. the most frequently identified subtyp ...201627010791
detection of reassortant avian influenza a (h11n9) virus in environmental samples from live poultry markets in china.avian influenza viruses have caused human infection and posed the pandemic potential. live poultry markets are considered as a source of human infection with avian influenza viruses. avian influenza routine surveillance of live poultry markets is taken annually in china. we isolated the 2 h11n9 influenza virus from the surveillance program. to better understand the risk caused by these new viruses, we characterize the genetic and pathogenicity of the two viruses.201627268229
rapid genome sequencing and characterization of novel avian-origin influenza a h7n9 virus directly from clinical sample by semiconductor sequencing.recent outbreaks of severe pneumonia or acute respiratory distress syndrome have attracted much public interest. rapid and accurate diagnosis of the causative agent is key for an adequate response to suspected outbreaks.201526580409
[analysis of the genetic evolution of neuraminidases of influenza a subtype n9 viruses].this study analyzed the genetic evolution of neuraminidases (nas) of influenza a subtype n9 viruses with the aim of determining the genetic origin of the novel avian a/h7n9 influenza virus. the na sequences of influenza a subtype n9 viruses available from ncbi were used to construct a phylogenetic tree using the programs clustalx 2.0 and mega 6.0. this analysis indicated that the novel avian a/h7n9 influenza virus is located in the modern eurasian phylogenetic cluster. this cluster was then furt ...201526164938
novel human h7n9 influenza virus in china.outbreaks of h7n9 avian influenza in humans in 5 provinces and 2 municipalities of china have reawakened concern that avian influenza viruses may again cross species barriers to infect the human population and thereby initiate a new influenza pandemic. evolutionary analysis shows that human h7n9 influenza viruses originated from the h9n2, h7n3 and h11n9 avian viruses, and that it is as a novel reassortment influenza virus. this article reviews current knowledge on 11 subtypes of influenza a viru ...201424952971
novel multiplex assay platforms to detect influenza a hemagglutinin subtype-specific antibody responses for high-throughput and in-field applications.detections of influenza a subtype-specific antibody responses are often complicated by the presence of cross-reactive antibodies. we developed two novel multiplex platforms for antibody detection. the multiplexed magnetic fluorescence microsphere immunoassay (magpix) is a high-throughput laboratory-based assay. chembio dual path platform (dpp) is a portable and rapid test that could be used in the field.201728207986
progress of small molecular inhibitors in the development of anti-influenza virus agents.the influenza pandemic is a major threat to human health, and highly aggressive strains such as h1n1, h5n1 and h7n9 have emphasized the need for therapeutic strategies to combat these pathogens. influenza anti-viral agents, especially active small molecular inhibitors play important roles in controlling pandemics while vaccines are developed. currently, only a few drugs, which function as influenza neuraminidase (na) inhibitors and m2 ion channel protein inhibitors, are approved in clinical. how ...201728382157
pandemic and avian influenza a viruses in humans: epidemiology, virology, clinical characteristics, and treatment strategy.the intermittent outbreak of pandemic influenza and emergence of novel avian influenza a virus is worldwide threat. although most patients present with mild symptoms, some deteriorate to severe pneumonia and even death. great progress in the understanding of the mechanism of disease pathogenesis and a series of vaccines has been promoted worldwide; however, incidence, morbidity, and mortality remains high. to step up vigilance and improve pandemic preparedness, this article elucidates the virolo ...201728159162
human seasonal influenza a viruses induce h7n9-cross-reactive antibody-dependent cellular cytotoxicity (adcc) antibodies that are directed towards the nucleoprotein.antibodies that mediate antibody-dependent cellular cytotoxicity (adcc) against avian influenza virus subtypes including h7n9 and h5n1 have been detected in human sera. there are limited data on the presence of such cross-reactive adcc mediating antibodies (adcc-abs) in children and the viral target(s) of these abs are poorly understood. using high-throughput nk cell activation and nk cytotoxicity assays, we compared adcc-abs in sera collected from healthy infants (≤1 year), children (2-17 years ...201628011910
simultaneous detection of influenza a subtypes of h3n2 virus, pandemic (h1n1) 2009 virus and reassortant avian h7n9 virus in humans by multiplex one-step real-time rt-pcr assay.influenza a virus is a leading causative pathogen of human acute respiratory infection. recently, the co-circulation of pandemic (h1n1) 2009 and seasonal h3n2 viruses was reported, and sporadic cases with reassortant avian h7n9 virus are continually reported in china. we aimed to establish a multiplex one-step real-time reverse transcription-polymerase chain reaction (rrt-pcr) assay to simultaneously detect and discriminate flua subtypes, including human seasonal h3n2 virus, pandemic (h1n1) 2009 ...201627995031
generation and characterisation of monoclonal antibodies specific to avian influenza h7n9 haemagglutinin protein.emerging virulent strains of influenza virus pose a serious public health threat with potential pandemic consequences. a novel avian influenza virus, h7n9, breached the species barrier from infected domestic poultry to humans in 2013 in china. since then, it has caused numerous infections in humans with a close contact to poultry.201727934828
nuclear magnetic resonance and molecular dynamics simulation of the interaction between recognition protein h7 of the novel influenza virus h7n9 and glycan cell surface receptors.avian influenza a viruses, which can also propagate between humans, present serious pandemic threats, particularly in asia. the specificity (selectivity) of interactions between the recognition protein hemagglutinin (ha) of the virus capsid and the glycoconjugates of host cells also contributes to the efficient spread of the virus by aerosol between humans. some avian origin viruses, such as h1n1 (south carolina 1918), have improved their selectivity for human receptors by mutation in the ha rec ...201627933797
pb1-f2 peptide derived from avian influenza a virus h7n9 induces inflammation via activation of the nlrp3 inflammasome.the emergence of avian h7n9 influenza a virus in humans with associated high mortality has highlighted the threat of a potential pandemic. fatal h7n9 infections are characterized by hyperinflammation and increased cellular infiltrates in the lung. currently there are limited therapies to address the pathologies associated with h7n9 infection and the virulence factors that contribute to these pathologies. we have found that pb1-f2 derived from h7n9 activates the nlrp3 inflammasome and induces lun ...201727913620
cardiac complications associated with the influenza viruses a subtype h7n9 or pandemic h1n1 in critically ill patients under intensive care.the clinical presentations and disease courses of patients hospitalized with either influenza a virus subtype h7n9 (h7n9) or 2009 pandemic h1n1 influenza virus were compared in a recent report, but associated cardiac complications remain unclear. the present retrospective study investigated whether cardiac complications in critically ill patients with h7n9 infections differed from those infected with the pandemic h1n1 influenza virus strain.201727912070
differential nucleocytoplasmic shuttling of the nucleoprotein of influenza a viruses and association with host tropism.the nucleoprotein (np) of influenza a virus plays a crucial role in virus replication, infectivity, and host adaptation. as a major component of the viral ribonucleoprotein complexes (vrnp), np initiates vrnp shuttling between the nucleus and cytoplasm in the host cell. however, the characteristics of the nucleocytoplasmic shuttling of np from h1n1 influenza a virus still remain unclear. in the present study, the subcellular localization and the related key residues of the h1n1 influenza virus n ...201727862840
identification of a novel small-molecule compound targeting the influenza a virus polymerase pb1-pb2 interface.the pb1 c-terminal domain and pb2 n-terminal domain interaction of the influenza a polymerase, which modulates the assembly of pb1 and pb2 subunits, may serve as a valuable target for the development of novel anti-influenza therapeutics. in this study, we performed a systematic screening of a chemical library, followed by the antiviral evaluation of primary hits and their analogues. eventually, a novel small-molecule compound pp7 that abrogated the pb1-pb2 association and impaired viral polymera ...201727840201
genotyping and detection of common avian and human origin-influenza viruses using a portable chemiluminescence imaging microarray.influenza viruses are divided into three types, a, b, and c. human influenza a and b viruses can cause seasonal epidemics, but influenza c causes only a mild respiratory illness. influenza a virus can infect various host species. in 2013, human-infectious avian influenza a (h7n9) was first reported in china. by the second week of 2014, there were 210 laboratory-confirmed human cases in the country, and the mortality rate eventually reached 22 %. rapid and accurate diagnosis of influenza viruses ...201627822445
constitutively expressed ifitm3 protein in human endothelial cells poses an early infection block to human influenza viruses.a role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. as the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. we found that a subset of avian influenza viruses, including potentially pandemic h5n1, h7n9, and h9n2 viruses, could infect huma ...201627707929
pandemic (h1n1) 2009 influenza virus infection in a survivor who has recovered from severe h7n9 virus infection, china.we firstly report a patient who presented with severe complications after infection with influenza a(h1n1) pdm2009, more than 1 year after recovery from severe h7n9 virus infections. the population of patients who recovered from severe h7n9 infections might be at a higher risk to suffer severe complications after seasonal influenza infections, and they should be included in the high-risk populations recommended to receive seasonal influenza vaccination.201627757100
focal adhesion kinase (fak) regulates polymerase activity of multiple influenza a virus subtypes.influenza a viruses (iavs) cause numerous pandemics and yearly epidemics resulting in ~500,000 annual deaths globally. iav modulates cellular signaling pathways at every step of the infection cycle. focal adhesion kinase (fak) has been shown to play a critical role in endosomal trafficking of influenza a viruses, yet it is unclear how fak kinase activity regulates iav replication. using mini-genomes derived from h1n1, h5n1 and h7n9 viruses, we dissected rna replication by iavs independent of vir ...201627743963
cross-immunity against avian influenza a(h7n9) virus in the healthy population is affected by antigenicity-dependent substitutions.the emergence of infections by the novel avian influenza a(h7n9) virus has posed a threat to human health. cross-immunity between a(h7n9) and other heterosubtypic influenza viruses affected by antigenicity-dependent substitutions needs to be investigated.201627738054
human monoclonal antibody 81.39a effectively neutralizes emerging influenza a viruses of group 1 and 2 hemagglutinins.the pandemic threat posed by emerging zoonotic influenza a viruses necessitates development of antiviral agents effective against various antigenic subtypes. human monoclonal antibody (hmab) targeting the hemagglutinin (ha) stalk offers a promising approach to control influenza virus infections. here, we investigated the ability of the hmab 81.39a to inhibit in vitro replication of human and zoonotic viruses, representing 16 ha subtypes. the majority of viruses were effectively neutralized by 81 ...201627630240
peptide-mediated interference of pb2-eif4g1 interaction inhibits influenza a viruses' replication in vitro and in vivo.influenza viruses are obligate parasites that hijack the host cellular system. previous results have shown that the influenza virus pb2 subunit confers a dependence of host eukaryotic translation initiation factor 4-γ 1 (eif4g1) for viral mrna translation. here, we demonstrated that peptide-mediated interference of the pb2-eif4g1 interaction inhibited virus replication in vitro and in vivo. remarkably, intranasal administration of the peptide provided 100% protection against lethal challenges of ...201627626099
effects of ha and na glycosylation pattern changes on the transmission of avian influenza a(h7n9) virus in guinea pigs.avian influenza h7n9 virus has posed a concern of potential human-to-human transmission by resulting in seasonal virus-like human infection cases. to address the issue of sustained human infection with the h7n9 virus, here we investigated the effects of hemagglutinin (ha) and neuraminidase (na) n-linked glycosylation (nlg) patterns on influenza virus transmission in a guinea pig model. based on the nlg signatures identified in the ha and na genetic sequences of h7n9 viruses, we generated nlg mut ...201627613087
cross-reactive antibodies against h7n9 and h5n1 avian influenza viruses in thai population.avian influenza h5n1 and h7n9 viruses have jumped across species from avian to humans and become a threat to public health. not much is known about pre-existing cross-reactive antibodies against these avian viruses in human population.201627543728
novel residues in the pa protein of avian influenza h7n7 virus affect virulence in mammalian hosts.to evaluate the pathogenicity, a highly pathogenic avian influenza h7n7 virus (a/netherlands/219/03) isolated from human was passaged in mice. a mutant virus (mh7n7) with attenuated virulence was isolated from mouse lung, which had a 3-log higher mld50 than the wild-type virus (wh7n7). sequence analysis and reverse genetics study revealed that mutations in pa account for the compromised viral replication in mammalian cells and mice. a mini-genome assay demonstrated that pa mutations p103h and s6 ...201627525812
pains and gains from china's experiences with emerging epidemics: from sars to h7n9.over the recent decades, china experienced several emerging virus outbreaks including those caused by the severe acute respiratory syndrome- (sars-) coronavirus (cov), h5n1 virus, and h7n9 virus. the sars tragedy revealed faults in china's infectious disease prevention system, propelling the chinese government to enact reforms that enabled better combating of the subsequent h1n1 and h7n9 avian flu epidemics. the system is buttressed by three fundamental, mutually reinforcing components: (1) endu ...201627525272
preexisting antibody-dependent cellular cytotoxicity-activating antibody responses are stable longitudinally and cross-reactive responses are not boosted by recent influenza exposure.cross-reactive influenza virus-specific antibody-dependent cellular cytotoxicity (adcc)-activating antibodies are readily detected in healthy adults. however, little is known about the kinetics of these adcc responses. we used retrospective serial blood samples from healthy donors to investigate this topic. all donors had adcc responses against 2009 pandemic influenza a(h1n1) virus (a[h1n1]pdm09) and avian influenza a(h7n9) virus hemagglutinins (has) despite being seronegative for these viruses ...201627493238
neutralization and binding profile of monoclonal antibodies generated against influenza a h1n1 viruses.monoclonal antibodies (mabs) provide scope for the development of better therapeutics and diagnostic tools. herein, we describe the binding and neutralization profile(s) for a panel of murine mabs generated against influenza a h1n1 viruses elicited by immunization with pandemic h1 recombinant hemagglutinin (rha)/whole virus or seasonal h1 rha. neutralizing mabs, ma-2070 and ma-m, were obtained after pandemic a/california/07/2009 (h1n1) virus/rha immunization(s). both mabs reacted specifically wi ...201627463230
a novel endonuclease inhibitor exhibits broad-spectrum anti-influenza virus activity in vitro.antiviral drugs are important in preventing and controlling influenza, particularly when vaccines are ineffective or unavailable. a single class of antiviral drugs, the neuraminidase inhibitors (nais), is recommended for treating influenza. the limited therapeutic options and the potential risk of antiviral resistance are driving the search for additional small-molecule inhibitors that act on influenza virus proteins. the acid polymerase (pa) of influenza viruses is a promising target for new an ...201627381402
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