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mild infection of a novel h7n9 avian influenza virus in children in shanghai. 201326038475
human h7n9 avian influenza virus infection: a review and pandemic risk assessment.china is undergoing a recent outbreak of a novel h7n9 avian influenza virus (nh7n9) infection that has thus far involved 132 human patients, including 37 deaths. the nh7n9 virus is a reassortant virus originating from the h7n3, h7n9 and h9n2 avian influenza viruses. nh7n9 isolated from humans contains features related to adaptation to humans, including a q226l mutation in the hemagglutinin cleavage site and e627k and d701n mutations in the pb2 protein. live poultry markets provide an environment ...201326038484
infection of inbred balb/c and c57bl/6 and outbred institute of cancer research mice with the emerging h7n9 avian influenza virus.a new avian-origin influenza virus a (h7n9) recently crossed the species barrier and infected humans; therefore, there is an urgent need to establish mammalian animal models for studying the pathogenic mechanism of this strain and the immunological response. in this study, we attempted to develop mouse models of h7n9 infection because mice are traditionally the most convenient models for studying influenza viruses. we showed that the novel a (h7n9) virus isolated from a patient could infect inbr ...201326038485
rapidly produced sam(®) vaccine against h7n9 influenza is immunogenic in mice.the timing of vaccine availability is essential for an effective response to pandemic influenza. in 2009, vaccine became available after the disease peak, and this has motivated the development of next generation vaccine technologies for more rapid responses. the sam(®) vaccine platform, now in pre-clinical development, is based on a synthetic, self-amplifying mrna, delivered by a synthetic lipid nanoparticle (lnp). when used to express seasonal influenza hemagglutinin (ha), a sam vaccine elicit ...201326038486
drug susceptibility profile and pathogenicity of h7n9 influenza virus (anhui1 lineage) with r292k substitution.neuraminidase inhibitors (nais) are the only available licensed therapeutics against human h7n9 influenza virus infections. the emergence of nai-resistant variants of h7n9viruses with an na r292k mutation poses a therapeutic challenge. a comprehensive understanding of the susceptibility of these viruses to clinically available nais, non-nais and their combinations is crucial for effective treatment. in this study, by using limited serial passage and plaque purification, an r292k variant of the a ...201426038501
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
the diversity of avian influenza virus subtypes in live poultry markets before and during the second wave of a(h7n9) infections in hangzhou, china. 201526038765
an h5n1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with h7n9 influenza virus.in march 2013, a patient infected with a novel avian influenza a h7n9 virus was reported in china. since then, there have been 458 confirmed infection cases and 177 deaths. the virus contains several human-adapted markers, indicating that h7n9 has pandemic potential. the outbreak of this new influenza virus highlighted the need for the development of universal influenza vaccines. previously, we demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (m2e) of the h ...201526038770
erratum: h7n9 avian influenza virus - search and re-search.[this corrects the article doi: 10.1038/emi.2013.18.].201326039114
erratum: a fatal case caused by novel h7n9 avian influenza a virus in china.[this corrects the article doi: 10.1038/emi.2013.22.].201326039226
erratum: human h7n9 avian influenza virus infection: a review and pandemic risk assessment.[this corrects the article doi: 10.1038/emi.2013.48.].201326039439
[on-microchip pcr for detection of influenza a viruses subtypes, circulating in the human population].a oligonucleotide microchip was developed for revealing influenza a viruses subtypes, circulating in human population: pandemic h1n1 swine influenza viruses, seasonal h1n1, h2n2, h3n2, h5n1, h9n2, h7n9. typing of influenza virus was performed by on-microchip pcr. we used immobilized primers-probes selected for the neuraminidase gene that allows determining both subtype of neuraminidase and subtype of hemagglutinin.201526050481
the intranasal application of zanamivir and carrageenan is synergistically active against influenza a virus in the murine model.carrageenan is a clinically proven and marketed compound for the treatment of viral upper respiratory tract infections. as infections caused by influenza virus are often accompanied by infections with other respiratory viruses the combination of a specific anti-influenza compound with the broadly active antiviral polymer has huge potential for the treatment of respiratory infections. thus, the combination of the specific anti-influenza drug zanamivir together with carrageenan in a formulation su ...201526053018
emergence of h7n9 influenza a virus resistant to neuraminidase inhibitors in nonhuman primates.the number of patients infected with h7n9 influenza virus has been increasing since 2013. we examined the efficacy of neuraminidase (na) inhibitors and the efficacy of a vaccine against an h7n9 influenza virus, a/anhui/1/2013 (h7n9), isolated from a patient in a cynomolgus macaque model. na inhibitors (oseltamivir and peramivir) barely reduced the total virus amount because of the emergence of resistant variants with r289k or i219t in na [residues 289 and 219 in n9 of a/anhui/1/2013 (h7n9) corre ...201526055368
intranasal immunization with pressure inactivated avian influenza elicits cellular and humoral responses in mice.influenza viruses pose a serious global health threat, particularly in light of newly emerging strains, such as the avian influenza h5n1 and h7n9 viruses. vaccination remains the primary method for preventing acquiring influenza or for avoiding developing serious complications related to the disease. vaccinations based on inactivated split virus vaccines or on chemically inactivated whole virus have some important drawbacks, including changes in the immunogenic properties of the virus. to induce ...201526056825
a live attenuated vaccine prevents replication and transmission of h7n9 virus in mammals.the continued spread of the newly emerged h7n9 viruses among poultry in china, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. an mf59-adjuvant h7n9 inactivated vaccine is reported to be well-tolerated and immunogenic in humans; however a study in ferrets indicated that while a single dose of the inactivated h7n9 vaccine reduced disease severity, it did not prevent virus replication a ...201526058711
the role of c5a in acute lung injury induced by highly pathogenic viral infections.the complement system, an important part of innate immunity, plays a critical role in pathogen clearance. unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ali) induced by highly pathogenic virus including influenza a viruses h5n1, h7n9, and severe acute respiratory syndrome (sars) coronavirus. in highly pathogenic virus-induced acute lung diseases, high levels of chemotactic and anaphylatoxic c5a were produced as a result of excessive c ...201526060601
radiological features of human infection with avian influenza a h7n9 virus: a report of three cases.human infection with avian influenza a h7n9 virus has emerged in china with high morbidity rates. patients usually present with severe and rapidly progressive pneumonia. therefore, radiological findings are important to diagnose and evaluate disease severity. the clinical characteristics of three new cases of h7n9 virus infection were analyzed, especially the radiological findings, and previously published studies regarding h7n9 virus infection were summarized. ground-glass opacification and are ...201426060749
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
a simplified sanger sequencing method for full genome sequencing of multiple subtypes of human influenza a viruses.full genome sequencing of influenza a viruses (iav), including those that arise from annual influenza epidemics, is undertaken to determine if reassorting has occurred or if other pathogenic traits are present. traditionally iav sequencing has been biased toward the major surface glycoproteins haemagglutinin and neuraminidase, while the internal genes are often ignored. despite the development of next generation sequencing (ngs), many laboratories are still reliant on conventional sanger sequenc ...201526071334
influenza a(h7n9) virus acquires resistance-related neuraminidase i222t substitution when infected mallards are exposed to low levels of oseltamivir in water.influenza a virus (iav) has its natural reservoir in wild waterfowl, and new human iavs often contain gene segments originating from avian iavs. treatment options for severe human influenza are principally restricted to neuraminidase inhibitors (nais), among which oseltamivir is stockpiled in preparedness for influenza pandemics. there is evolutionary pressure in the environment for resistance development to oseltamivir in avian iavs, as the active metabolite oseltamivir carboxylate (oc) passes ...201526077257
host genes and influenza pathogenesis in humans: an emerging paradigm.the emergence of the pandemic influenza virus a(h1n1)pdm09 in 2009 and avian influenza virus a(h7n9) in 2013 provided unique opportunities for assessing genetic predispositions to severe disease because many patients did not have any underlying risk factor or neutralizing antibody against these agents, in contrast to seasonal influenza viruses. high-throughput screening platforms and large human or animal databases from international collaborations allow rapid selection of potential candidate ge ...201526079652
[predicating risk area of human infection with avian influenza a (h7n9) virus by using early warning model in china].to establish a risk early warning model of human infection with avian influenza a (h7n9) virus and predict the area with high risk of the outbreak of h7n9 virus infection.201526080636
[investigation of a family clustering of human infection with avian influenza a (h7n9) virus in nanning, guangxi].to understand the transmission mode of human infection with avian influenza a (h7n9) virus.201526080638
newly emergent highly pathogenic h5n9 subtype avian influenza a virus.the novel h7n9 avian influenza virus (aiv) was demonstrated to cause severe human respiratory infections in china. here, we examined poultry specimens from live bird markets linked to human h7n9 infection in hangzhou, china. metagenomic sequencing revealed mixed subtypes (h5, h7, h9, n1, n2, and n9). subsequently, aiv subtypes h5n9, h7n9, and h9n2 were isolated. evolutionary analysis showed that the hemagglutinin gene of the novel h5n9 virus originated from a/muscovy duck/vietnam/lbm227/2012 (h5 ...201526085150
single fluorescence channel-based multiplex detection of avian influenza virus by quantitative pcr with intercalating dye.since its invention in 1985 the polymerase chain reaction (pcr) has become a well-established method for amplification and detection of segments of double-stranded dna. incorporation of fluorogenic probe or dna intercalating dyes (such as sybr green) into the pcr mixture allowed real-time reaction monitoring and extraction of quantitative information (qpcr). probes with different excitation spectra enable multiplex qpcr of several dna segments using multi-channel optical detection systems. here ...201526088868
h7n9 t-cell epitopes that mimic human sequences are less immunogenic and may induce treg-mediated tolerance.avian-origin h7n9 influenza is a novel influenza a virus (iav) that emerged in humans in china in 2013. using immunoinformatics tools, we identified several h7n9 t cell epitopes with t cell receptor (tcr)-facing residues identical to those of multiple epitopes from human proteins. we hypothesized that host tolerance to these peptides may impair t helper response and contribute to the low titer, weak hemagglutination inhibiting (hi) antibody responses and diminished seroconversion rates that have ...201526090577
iscomatrix™ adjuvant promotes epitope spreading and antibody affinity maturation of influenza a h7n9 virus like particle vaccine that correlate with virus neutralization in humans.in a previously reported phase i clinical trial, subjects vaccinated with two doses of an unadjuvanted h7n9 virus like particle (vlp) vaccine responded poorly (15.6% seroconversion rates with 45μg hemagglutinin (ha) dose). in contrast, 80.6% of subjects receiving h7n9 vlp vaccine (5μg ha) with iscomatrix™ adjuvant developed hemagglutination-inhibition (hi) responses. to better understand the role of adjuvant, complete antibody epitope repertoires of post-vaccination sera were investigated using ...201526093202
influenza virus activating host proteases: identification, localization and inhibitors as potential therapeutics.cellular proteases are reponsible for activation of influenza virus hemagglutinin (ha) in epithelial tissues of the respiratory tract. the trans-golgi network (tgn) is the main subcellular compartment where ha cleavage occurs during its biosynthesis. the proteolytic ha cleavage is an indispensable prerequisite for the fusion of viral with endosomal membrane and the delivery of the virus genome into the cell. both, the structure and accessibility of the ha cleavage site determine the responsible ...201526095298
computational analysis of antigenic epitopes of avian influenza a (h7n9) viruses.influenza virus can rapidly change its antigenicity, via mutation in the hemagglutinin (ha) protein, to evade host immunity. the emergence of the novel human-infecting avian h7n9 virus in china has caused widespread concern. however, evolution of the antigenicity of this virus is not well understood. here, we inferred the antigenic epitopes of the ha protein from all h7 viruses, based on the five well-characterized ha epitopes of the human h3n2 virus. by comparing the two major h7 phylogenetic l ...201526100010
as03-adjuvanted h7n1 detergent-split virion vaccine is highly immunogenic in unprimed mice and induces cross-reactive antibodies to emerged h7n9 and additional h7 subtypes.avian h7 is one of several influenza a virus subtypes that have the potential to cause pandemics. herein we describe preclinical results following administration of an investigational h7n1 inactivated detergent-split virion vaccine adjuvanted with the as03 adjuvant system. the adjuvanted h7n1 vaccine was highly immunogenic compared to the non-adjuvanted h7n1 vaccine in unprimed mice with less than 100ng of hemagglutinin antigen per dose. in addition, compared to the non-adjuvanted vaccine, the a ...201526100923
a case report of avian influenza h7n9 killing a young doctor in shanghai, china.the novel avian influenza h7n9 virus has caused severe diseases in humans in eastern china since the spring of 2013. on january 18(th) 2014, a doctor working in the emergency department of a hospital in shanghai died of h7n9 virus infection. to understand possible reasons to explain this world's first fatal h7n9 case of a health care worker (hcw), we summarize the clinical presentation, epidemiological investigations, laboratory results, and prevention and control policies and make important rec ...201526101082
[the first human case of infection of highly pathogenic h7n9 avian influenza virus in guizhou province]. 201526138430
the role of live poultry movement and live bird market biosecurity in the epidemiology of influenza a (h7n9): a cross-sectional observational study in four eastern china provinces.a new reassortant influenza a (h7n9) virus emerged early 2013 in eastern china. exposure to h7n9 infected poultry at live bird markets (lbm) was implicated as the main risk factor for human infection. we aimed to identify the role of lbm biosecurity indicators and poultry movement in the affected areas.201526149187
[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 ranking system for identifying efficacious anti-influenza virus pb2 inhibitors.through antigenic drift and shifts, influenza virus infections continue to be an annual cause of morbidity in healthy populations and of death among elderly and at-risk patients. the emergence of highly pathogenic avian influenza viruses such as h5n1 and h7n9 and the rapid spread of the swine-origin h1n1 influenza virus in 2009 demonstrate the continued need for effective therapeutic agents for influenza. while several neuraminidase inhibitors have been developed for the treatment of influenza v ...201526169418
surveillance of influenza a virus and its subtypes in migratory wild birds of nepal.nepal boarders india and china and all three countries lie within the central asian flyway for migratory birds. novel influenza a h7n9 caused human fatalities in china in 2013. subclinical infections of influenza a h7n9 in birds and the potential for virus dispersal by migratory birds prompted this study to assess avian h7n9 viral intrusion into nepal. surveillance of influenza a virus in migratory birds was implemented in early 2014 with assistance from the food and agricultural organization (f ...201526176773
evaluation and application of a one-step duplex real-time reverse transcription polymerase chain reaction assay for the rapid detection of influenza a (h7n9) virus from poultry samples.in china, a novel reassortant influenza a (h7n9) virus, which has caused 435 cases of human infection, has recently emerged. most cases of human infections with the h7n9 virus are known to be associated with a poultry farm and live-poultry markets. in this study, a one-step duplex real-time reverse transcription polymerase chain reaction (rrt-pcr) assay was developed for the simultaneous detection of the hemagglutinin (ha) and neuraminidase (na) genes of the h7n9 virus for effective surveillance ...201526179621
repurposing kinase inhibitors as antiviral agents to control influenza a virus replication.influenza a virus (iav) infection causes seasonal epidemics of contagious respiratory illness that causes substantial morbidity and some mortality. regular vaccination is the principal strategy for controlling influenza virus, although vaccine efficacy is variable. iav antiviral drugs are available; however, substantial drug resistance has developed to two of the four currently fda-approved antiviral drugs. thus, new therapeutic approaches are being sought to reduce the burden of influenza-relat ...201526192013
social media messages in an emerging health crisis: tweeting bird flu.limited research has examined the messages produced about health-related crises on social media platforms and whether these messages contain content that would allow individuals to make sense of a crisis and respond effectively. this study uses the crisis and emergency risk communication (cerc) framework to evaluate the content of messages sent via twitter during an emerging crisis. using manual and computer-driven content analysis methods, the study analyzed 25,598 tweets about the h7n9 virus t ...201626192209
development of framework for assessing influenza virus pandemic risk.although predicting which influenza virus subtype will cause the next pandemic is not yet possible, public health authorities must continually assess the pandemic risk associated with animal influenza viruses, particularly those that have caused infections in humans, and determine what resources should be dedicated to mitigating that risk. to accomplish this goal, a risk assessment framework was created in collaboration with an international group of influenza experts. compared with the previous ...201526196098
effect of varying doses of a monovalent h7n9 influenza vaccine with and without as03 and mf59 adjuvants on immune response: a randomized clinical trial.human infections with the avian influenza a(h7n9) virus were first reported in china in 2013 and continue to occur. hemagglutinin h7 administered alone is a poor immunogen necessitating evaluation of adjuvanted h7n9 vaccines.201526197184
transmission of h7n9 influenza viruses with a polymorphism at pb2 residue 627 in chickens and ferrets.poultry exposure is a major risk factor for human h7n9 zoonotic infections, for which the mode of transmission remains unclear. we studied the transmission of genetically related poultry and human h7n9 influenza viruses differing by four amino acids, including the host determinant pb2 residue 627. a/silkie chicken/hk/1772/2014 (sck1772) and a/hk/3263/14 (hk3263) replicated to comparable titers in chickens, with superior oropharyngeal over cloacal shedding; both viruses transmitted efficiently am ...201526202239
the pandemic potential of avian influenza a(h7n9) virus: a review.in march 2013 the first cases of human avian influenza a(h7n9) were reported to the world health organization. since that time, over 650 cases have been reported. infections are associated with considerable morbidity and mortality, particularly within certain demographic groups. this rapid increase in cases over a brief time period is alarming and has raised concerns about the pandemic potential of the h7n9 virus. three major factors influence the pandemic potential of an influenza virus: (1) it ...201526205078
recombinant h7 hemagglutinin forms subviral particles that protect mice and ferrets from challenge with h7n9 influenza virus.a novel avian-origin influenza a h7n9 virus emerged in china in 2013 and continues to cause sporadic human infections with mortality rates approaching 35%. currently there are no approved human vaccines for h7n9 virus. recombinant approaches including hemagglutinin (ha) and virus-like particles (vlps) have resulted in experimental vaccines with advantageous safety and manufacturing characteristics. while high immunogenicity of vlp vaccines has been attributed to the native conformation of ha arr ...201526207590
diagnostics-in-a-suitcase: development of a portable and rapid assay for the detection of the emerging avian influenza a (h7n9) virus.in developing countries, equipment necessary for diagnosis is only available in few central laboratories, which are less accessible and of limited capacity to test large numbers of incoming samples. moreover, the transport conditions of samples are inadequate, therefore leading to unreliable results.201526209370
extra-pulmonary viral shedding in h7n9 avian influenza patients.the clinical features of avian-origin influenza virus a (h7n9) virus infection have been extensively characterized, but viral rna detection in extra-pulmonary samples has seldom been studied.201526209373
epidemiology of human influenza a(h7n9) infection in hong kong.we conducted a case series study to review the epidemiology of human influenza a(h7n9) infection reported in hong kong.201526220305
proinflammatory effects of the hemagglutinin protein of the avian influenza a (h7n9) virus and microrna‑mediated homeostasis response in thp‑1 cells.the pathology and immunological responses to hemagglutinin (ha) from h7n9 avian influenza viruses in humans remain unclear. the present study aimed to investigate the proinflammatory activity of the ha protein obtained from h7n9 viruses and the mechanisms underlying the homeostasis of micrornas (mirnas) in response to inflammatory stimuli. the expression of proinflammatory factors and mirnas was assayed in the thp‑1 cells using reverse transcription‑quantitative polymerase chain reaction. result ...201526238163
optimisations and challenges involved in the creation of various bioluminescent and fluorescent influenza a virus strains for in vitro and in vivo applications.bioluminescent and fluorescent influenza a viruses offer new opportunities to study influenza virus replication, tropism and pathogenesis. to date, several influenza a reporter viruses have been described. these strategies typically focused on a single reporter gene (either bioluminescent or fluorescent) in a single virus backbone. however, whilst bioluminescence is suited to in vivo imaging, fluorescent viruses are more appropriate for microscopy. therefore, the idea l reporter virus varies dep ...201526241861
serum samples from middle-aged adults vaccinated annually with seasonal influenza vaccines cross-neutralize some potential pandemic influenza viruses.we examined serum samples from adults ages 48-64 who received multiple seasonal influenza vaccines from 2004 to 2009 for cross-neutralizing antibodies to potential pandemic strains. using pseudoviruses bearing various hemagglutinins (ha-pseudoviruses), we found serum neutralization titers (≥160) in 100% against a/japan/305/1957 (h2n2), 53% against a/hong kong/1073/99 (h9n2), 56% against the h3n2 variant a/indiana/08/11 (h3n2v), 11% against a/hong kong/g9/97 (h9n2), and 36% a/chicken/hong kong/sf ...201626243315
characterization of humoral responses induced by an h7n9 influenza virus-like particle vaccine in balb/c mice.in april 2013, human infections with a novel avian influenza (h7n9) virus emerged in china. it has caused serious concerns for public health throughout the world. however, there is presently no effective treatment, and an a (h7n9) h7 subtype influenza vaccine is not available. vaccination with virus-like particles (vlps) has showed considerable promise for many other subtype influenza viruses. to produce h7n9 vlps, full length, unmodified hemagglutinin (ha), neuraminidase (na), and matrix1 (m1) ...201526248076
phylogenetic and molecular analysis of an h7n7 avian influenza virus isolated in east dongting lake in 2012.in march 2012, an h7n7 subtype avian influenza virus (aiv) named a/wild goose/dongting/pc0360/2012 (h7n7) (dt/pc0360) was recovered from a wild goose in east dongting lake. we performed whole-genome sequencing of the isolate, and analyzed the phylogenetic and molecular characterization.201526248736
establishment of functional influenza virus-specific cd8(+) t cell memory pools after intramuscular immunization.the emergence of the avian-origin influenza h7n9 virus and its pandemic potential has highlighted the ever-present need to develop vaccination approaches to induce cross-protective immunity. in this study, we examined the establishment of cross-reactive cd8(+) t cell immunity in mice following immunization with live a/puerto rico/8/1934 (pr8; h1n1) influenza virus via two non-productive inoculation routes. we found that immunization via the intramuscular (im) route established functional influen ...201526277069
rapid and quantitative detection of avian influenza a(h7n9) virions in complex matrices based on combined magnetic capture and quantum dot labeling.avian influenza a(h7n9) virus, which emerged in china in the spring of 2013, has infected hundreds of people and resulted in many deaths. herein, a rapid and quantitative assay is proposed for the one-step detection of h7n9 virions. immunomagnetic nanospheres (imns) and antibody-conjugated quantum dots (ab-qds) are simultaneously employed to capture and identify the target virus, leading to a high efficiency, good specificity, and strong anti-interference ability. moreover, this reliable detecti ...201526280101
a broadly neutralizing human monoclonal antibody is effective against h7n9.emerging strains of influenza represent a significant public health threat with potential pandemic consequences. of particular concern are the recently emerged h7n9 strains which cause pneumonia with acute respiratory distress syndrome. estimates are that nearly 80% of hospitalized patients with h7n9 have received intensive care unit support. vis410, a human antibody, targets a unique conserved epitope on influenza a. we evaluated the efficacy of vis410 for neutralization of group 2 influenza st ...201526283346
the therapeutic effect of pamidronate on lethal avian influenza a h7n9 virus infected humanized mice.a novel avian influenza virus h7n9 infection occurred among human populations since 2013. although the lack of sustained human-to-human transmission limited the epidemics caused by h7n9, the late presentation of most patients and the emergence of neuraminidase-resistant strains made the development of novel antiviral strategy against h7n9 in urgent demands. in this study, we evaluated the potential of pamidronate, a pharmacological phosphoantigen that can specifically boost human vδ2-t-cell, on ...201526285203
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
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
third wave of influenza a(h7n9) virus from poultry, guangdong province, china, 2014-2015.fourteen influenza a(h7n9) viruses were isolated from poultry or the environment in live poultry markets in guangdong province, china during 2014-2015. phylogenetic analysis showed that all viruses were descended from viruses of the second wave of influenza a(h7n9) virus infections during 2013. these viruses can be divided into 2 branches.201526291620
living poultry markets in rural area: human infection with h7n9 virus re-emerges in zhejiang province, china, in winter 2014.avian influenza a h7n9 virus, previously undetected in humans, has caused infections in many areas in china since february 2013. here we report the re-emergence of a case of h7n9 in rural jiaxing city, zhejiang province, in the winter of 2014.201526305813
virus replication kinetics and pathogenesis of infection with h7n9 influenza virus in isogenic guinea pigs upon intratracheal inoculation.since 2013, avian influenza viruses of subtype h7n9 have been transmitted from poultry to humans in china and caused severe disease. concerns persist over the pandemic potential of this virus and further understanding of immunity and transmission is required. the isogenic guinea pig model uniquely would allow for investigation into both. eighteen female isogenic guinea pigs 12-16 weeks were inoculated intratracheally with either a/h7n9 virus (n=12) or pbs (n=6) and sacrificed on days 2 and 7 pos ...201526307235
surveillance of avian h7n9 virus in various environments of zhejiang province, china before and after live poultry markets were closed in 2013-2014.to date, there have been a total of 637 laboratory-confirmed cases of human infection with avian influenza a (h7n9) virus across mainland china, with 28% (179/637) of these reported in zhejiang province. surveillance of avian h7n9 virus was conducted to investigate environmental contamination during h7n9 outbreaks. we sought to evaluate the prevalence of h7n9 in the environment, and the effects of poultry market closures on the incidence of human h7n9 cases.201526308215
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
adaptive mutations in pb2 gene contribute to the high virulence of a natural reassortant h5n2 avian influenza virus in mice.the highly pathogenic a/chicken/hebei/1102/2010 (hb10) h5n2 virus is a natural reassortant derived from circulating h5n1 and endemic h9n2 avian influenza viruses (aiv). to evaluate the potential of its interspecies transmission, we previously serially passaged the non-virulent hb10 virus in the mouse lung and obtained a high virulence variant (hb10-ma). genomic sequencing revealed five mutations (ha-s227n, pb2-q591k, pb2-d701n, pa-i554v and np-r351k) that distinguished hb10-ma virus from its par ...201526315686
sex differences in h7n9 influenza a virus pathogenesis.sex, gender and age have an impact on incidence and severity of several infectious diseases. here, we analyzed reported human cases of avian h7n9 influenza a virus infections for potential sex-dependent incidence and mortality. we report that females in their reproductive years display an increased tendency to die of h7n9 influenza than males (female-to-male ratio=1.2). next, we challenged this potential sex-dependent difference in influenza disease outcome using a mouse infection model. in gene ...201526319064
heterosubtypic immunity to h7n9 influenza virus in isogenic guinea pigs after infection with pandemic h1n1 virus.heterosubtypic immunity is defined as immune-mediated (partial) protection against an influenza virus induced by an influenza virus of another subtype to which the host has not previously been exposed. this cross-protective effect has not yet been demonstrated to the newly emerging avian influenza a viruses of the h7n9 subtype. here, we assessed the induction of protective immunity to these viruses by infection with a(h1n1)pdm09 virus in a newly developed guinea pig model. to this end, ten femal ...201526319067
on avian influenza epidemic models with time delay.after the outbreak of the first avian influenza a virus (h5n1) in hong kong in 1997, another avian influenza a virus (h7n9) crossed the species barrier in mainland china in 2013 and 2014 and caused more than 400 human cases with a death rate of nearly 40%. in this paper, we take account of the incubation periods of avian influenza a virus and construct a bird-to-human transmission model with different time delays in the avian and human populations combining the survival probability of the infect ...201526328909
development of high-yield influenza a virus vaccine viruses.vaccination is one of the most cost-effective ways to prevent infection. influenza vaccines propagated in cultured cells are approved for use in humans, but their yields are often suboptimal. here, we screened a/puerto rico/8/34 (pr8) virus mutant libraries to develop vaccine backbones (defined here as the six viral rna segments not encoding haemagglutinin and neuraminidase) that support high yield in cell culture. we also tested mutations in the coding and regulatory regions of the virus, and c ...201526334134
computational assay of zanamivir binding affinity with original and mutant influenza neuraminidase 9 using molecular docking.based upon molecular docking, this study aimed to find notable in silico neuraminidase 9 (na9) point mutations of the avian influenza a h7n9 virus that possess a zanamivir resistant property and to determine the lead compound capable of inhibiting these na9 mutations. seven amino acids (key residues) at the binding site of neuraminidase 9 responsible for zanamivir-na9 direct interactions were identified and 72 commonly occurring mutant na9 versions were created using the sybyl-x 2.0 software. th ...201526341387
testing the effect of internal genes derived from a wild-bird-origin h9n2 influenza a virus on the pathogenicity of an a/h7n9 virus.since 2013, avian influenza a(h7n9) viruses have diversified into multiple lineages by dynamically reassorting with other viruses, especially h9n2, in chinese poultry. despite concerns about the pandemic threat posed by h7n9 viruses, little is known about the biological properties of h7n9 viruses that may recruit internal genes from genetically distinct h9n2 viruses circulating among wild birds. here, we generated 63 h7n9 reassortants derived from an avian h7n9 and a wild-bird-origin h9n2 virus. ...201526344762
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
persistence of lymphocytopenia with ct abnormalities among patients with critical h7n9 swine-origin influenza a virus infection.h7n9 is an emerging pathogen with associated morbidity and mortality, and a broader understanding of the chest radiographic characteristics associated with human h7n9 infections is needed. this study was performed to determine the time course of recovery from lymphocytopenia and resolution of pneumonitis of critical h7n9 infection patients.201526345427
evaluation of commercial diagnostic assays for the specific detection of avian influenza a (h7n9) virus rna using a quality-control panel and clinical specimens in china.a novel avian influenza a h7n9-subtype virus emerged in china in 2013 and threatened global public health. commercial kits that specifically detect avian influenza a (h7n9) virus rna are urgently required to prepare for the emergence and potential pandemic of this novel influenza virus. the safety and effectiveness of three commercial molecular diagnostic assays were evaluated using a quality-control panel and clinical specimens collected from over 90 patients with confirmed avian influenza a (h ...201526361351
h7n9 influenza outbreak in china 2013: in silico analyses of conserved segments of the hemagglutinin as a basis for the selection of peptide vaccine targets.the sudden emergence of a human infecting strain of h7n9 influenza virus in china in 2013 leading to fatalities in about 30% of the cases has caused wide concern that additional mutations in the strain leading to human to human transmission could lead to a deadly pandemic. it may happen in a short time span as the outbreak of h7n9 is more and more recurrent, which implies that h7n9 evolution is speeding up. h7n9 flu strains were not known to infect humans before this attack in china in february ...201526364271
live poultry exposure and public response to influenza a(h7n9) in urban and rural china during two epidemic waves in 2013-2014.the novel influenza a(h7n9) virus has caused 2013 spring and 2013-2014 winter waves of human infections since its first emergence in china in march 2013. exposure to live poultry is a risk factor for h7n9 infection. public psychobehavioral responses often change during progression of an epidemic.201526367002
assessment of antiviral properties of peramivir against h7n9 avian influenza virus in an experimental mouse model.the h7n9 influenza virus causes a severe form of disease in humans. neuraminidase inhibitors, including oral oseltamivir and injectable peramivir, are the first choices of antiviral treatment for such cases; however, the clinical efficacy of these drugs is questionable. animal experimental models are essential for understanding the viral replication kinetics under the selective pressure of antiviral agents. this study demonstrates the antiviral activity of peramivir in a mouse model of h7n9 avia ...201526369969
retrospective study of risk factors for mortality in human avian influenza a(h7n9) cases in zhejiang province, china, march 2013 to june 2014.the influenza a(h7n9) virus causes a serious disease that threatens human health. fatalities associated with human infections caused by this virus are of great public health concern; however, the possible risk factors are not yet fully known.201526376223
protective efficacy of an inactivated vaccine against h9n2 avian influenza virus in ducks.wild ducks play an important role in the evolution of avian influenza viruses (aivs). domestic ducks in china are known to carry and spread h9n2 aivs that are thought to have contributed internal genes for the recent outbreak of zoonotic h7n9 virus. in order to protect animal and public health, an effective vaccine is urgently needed to block and prevent the spread of h9n2 virus in ducks. we developed an inactivated h9n2 vaccine (with adjuvant montanide isa 70vg) based on an endemic h9n2 aiv and ...201526377565
highly pathogenic h5n1 and novel h7n9 influenza a viruses induce more profound proteomic host responses than seasonal and pandemic h1n1 strains.influenza a viruses (iav) are important human and animal pathogens with potential for causing pandemics. iavs exhibit a wide spectrum of clinical illness in humans, from relatively mild infections by seasonal strains to acute respiratory distress syndrome during infections with some highly pathogenic avian influenza (hpai) viruses. in the present study, we infected a549 human cells with seasonal h1n1 (sh1n1), 2009 pandemic h1n1 (pdmh1n1), or novel h7n9 and hpai h5n1 strains. we used multiplexed ...201526381135
dual e627k and d701n mutations in the pb2 protein of a(h7n9) influenza virus increased its virulence in mammalian models.the ongoing avian h7n9 influenza outbreaks in china have caused significant human fatal cases and the virus is becoming established in poultry. mutations with potential to increase mammalian adaptation have occurred in the polymerase basic protein 2 (pb2) and other viral genes. here we found that dual 627k and 701n mutations could readily occur during transmission of the virus among ferrets via direct physical contact, and these mutations conferred higher polymerase activity and improved viral r ...201526391278
human infection and environmental contamination with avian influenza a (h7n9) virus in zhejiang province, china: risk trend across the three waves of infection.the third wave of h7n9 cases in china emerged in the second half of 2014. this study was conducted to identify the risk trends of h7n9 virus in human infections and environment contamination.201526392274
identification of conserved peptides comprising multiple t cell epitopes of matrix 1 protein in h1n1 influenza virus.cell mediated immune response plays a key role in combating viral infection and thus identification of new vaccine targets manifesting t cell mediated response may serve as an ideal approach for influenza vaccine. the present study involves the application of an immunoinformatics-based consensus approach for epitope prediction (three epitope prediction tools each for cd4+ and cd8+ t cell epitopes) and molecular docking to identify peptide sequences containing t cell epitopes using the conserved ...201526398199
effect of live poultry market closure on avian influenza a(h7n9) virus activity in guangzhou, china, 2014.we assessed the effect of closing live poultry markets in china on influenza a(h7n9) virus detection and viability. intensive sampling was carried out before, during, and after a 2-week citywide market closure; the markets were cleaned and disinfected at the beginning of the closure period. swab samples were collected at different sites within the markets and tested for h7n9 by real-time reverse transcription pcr and culture. during the closure, h7n9 viral rna detection and isolation rates in re ...201526402310
matrix-m adjuvated seasonal virosomal influenza vaccine induces partial protection in mice and ferrets against avian h5 and h7 challenge.there is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. it is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. in addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. an effective pre-pandemic vaccine is therefore required as a fir ...201526402787
generation and characterization of live attenuated influenza a(h7n9) candidate vaccine virus based on russian donor of attenuation.avian influenza a (h7n9) virus has emerged recently and continues to cause severe disease with a high mortality rate in humans prompting the development of candidate vaccine viruses. live attenuated influenza vaccines (laiv) are 6:2 reassortant viruses containing the ha and na gene segments from wild type influenza viruses to induce protective immune responses and the six internal genes from master donor viruses (mdv) to provide temperature sensitive, cold-adapted and attenuated phenotypes.201526405798
estimating the distribution of the incubation periods of human avian influenza a(h7n9) virus infections.a novel avian influenza virus, influenza a(h7n9), emerged in china in early 2013 and caused severe disease in humans, with infections occurring most frequently after recent exposure to live poultry. the distribution of a(h7n9) incubation periods is of interest to epidemiologists and public health officials, but estimation of the distribution is complicated by interval censoring of exposures. imputation of the midpoint of intervals was used in some early studies, resulting in estimated mean incub ...201526409239
normal human sera contain heat-sensitive factor(s) to enhance h7n9 influenza virus infection. 201626409904
h7n9 influenza virus is more virulent in ferrets than 2009 pandemic h1n1 influenza virus.the novel h7n9 influenza virus has been infecting humans in china since february 2013 and with a mortality rate of about 40%. this study compared the pathogenicity of the h7n9 and 2009 pandemic h1n1 influenza viruses in a ferret model, which shows similar symptoms to those of humans infected with influenza viruses. the h7n9 influenza virus caused a more severe disease than did the 2009 pandemic h1n1 influenza virus. all of the ferrets infected with the h7n9 influenza virus had died by 6 days aft ...201526421365
correction: evaluation of commercial diagnostic assays for the specific detection of avian influenza a (h7n9) virus rna using a quality-control panel and clinical specimens in china. 201526431524
plant-derived h7 vlp vaccine elicits protective immune response against h7n9 influenza virus in mice and ferrets.in march 2013, the chinese centre for disease control and prevention confirmed the first reported case of human infection with an avian influenza a h7n9 virus. infection with this virus often caused severe pneumonia and acute respiratory distress syndrome resulting in a case fatality rate >35%. the risk of pandemic highlighted, once again, the need for a more rapid and scalable vaccine response capability. here, we describe the rapid (19 days) development of a plant-derived vlp vaccine based on ...201526432915
in-silico structural analysis of the influenza a subtype h7n9 neuraminidase and molecular docking with different neuraminidase inhibitors.human infection with h7 influenza subtypes usually resulted in mild disease with a rare mortalities, however, human infection with the avian low pathogenic h7n9 influenza virus resulted in about 38.6 % human fatality. due to the new cross-species barrier of this virus subtype, there is an urgent need to better understand the susceptibility to commercially available antivirals and their relation to the structural changes of the viral neuraminidase. neuraminidases derived from 2013 h7n9, h5n1 and ...201526436118
pigeons are resistant to experimental infection with h7n9 avian influenza virus.to determine the susceptibility of pigeons to the newly emerged avian influenza virus subtype h7n9, we experimentally infected three different types of pigeons (meat, town, and racing) with two different doses (2 × 10(4) or 2 × 10(5) eid50) of h7n9 avian influenza virus a/chicken/china/2013 by either intranasal and intraocular inoculation (in + io) or intravenous injection (iv). in addition, the potential transmission of h7n9 to pigeons by direct close contact with experimentally infected pigeon ...201526443061
suboptimal humoral immune response against influenza a(h7n9) virus is related to its internal genes.influenza a(h7n9) virus pneumonia is associated with a high case fatality rate in humans. multiple viral factors have been postulated to account for the high virulence of the virus. it has been reported that patients with influenza a(h7n9) virus infection have relatively low titers of neutralizing antibodies compared to those with seasonal influenza virus infections. in this study, we compared serum hemagglutination inhibition (hi) and microneutralization (mn) antibody titers of mice challenged ...201526446420
live poultry market workers are susceptible to both avian and swine influenza viruses, guangdong province, china.guangdong province is recognized for dense populations of humans, pigs, poultry and pets. in order to evaluate the threat of viral infection faced by those working with animals, a cross-sectional, sero-epidemiological study was conducted in guangdong between december 2013 and january 2014. individuals working with swine, at poultry farms, or live poultry markets (lpm), and veterinarians, and controls not exposed to animals were enrolled in this study and 11 (4 human, 3 swine, 3 avian, and 1 cani ...201526476563
report on the second who integrated meeting on development and clinical trials of influenza vaccines that induce broadly protective and long-lasting immune responses: geneva, switzerland, 5-7 may 2014.on 5-7 may 2014, the world health organization (who) convened the second integrated meeting on "influenza vaccines that induce broadly protective and long-lasting immune responses". around 100 invited experts from academia, the vaccine industry, research and development funders, and regulatory and public health agencies attended the meeting. areas covered included mechanisms of protection in natural influenza-virus infection and vaccine-induced immunity, new approaches to influenza-vaccine desig ...201526478203
successful treatment of avian-origin influenza a (h7n9) infection using convalescent plasma.in january 2015, there was an outbreak of avian-origin influenza a (h7n9) virus in zhejiang province, china. a 45-year-old man was admitted to the first affiliated hospital of zhejiang university with a high fever that had lasted 7 days, chills, and a cough with yellow sputum. laboratory testing confirmed infection with the h7n9 virus, likely obtained from contact with poultry at a local live poultry market. a large dense shadow was apparent in the patient's left lung at the time of admission. t ...201526482389
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
protection against h7 subtype influenza virus infection in mice by passive transfer of neutralizing monoclonal antibody.h7 subtype influenza viruses pose serious threats to both the poultry industry and public health. recent human infections of avian h7n9 influenza viruses with substantial morbidity and mortality have raised concerns about this virus becoming a potential pandemic pathogen. neutralizing antibodies have been proven to be highly effective in blocking influenza virus infections. in this study, in order to develop an antibody-based immunoprophylaxis against h7 subtype influenza virus, we first generat ...201526492625
lung ultrasonography for the diagnosis of 11 patients with acute respiratory distress syndrome due to bird flu h7n9 infection.a novel reassortant avian-origin influenza a (h7n9) virus was found to infect three chinese residents, the first h7n9 infection in humans in asia. chest computed tomography (ct) for acute respiratory distress syndrome (ards) diagnosis is not only expensive but also exposes patients to radiation and might cause patients to be at risk of infection during transportation; in addition, chest radiography cannot be used to monitor the lung repeatedly in real time. therefore, the routine use of bedside ...201526503117
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