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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
[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
human infection with influenza a(h7n9) virus during 3 major epidemic waves, china, 2013-2015.since march 2013, a novel influenza a(h7n9) virus has caused 3 epidemic waves of human infection in mainland china. we analyzed data from patients with laboratory-confirmed influenza a(h7n9) virus infection to estimate the risks for severe outcomes after hospitalization across the 3 waves. we found that hospitalized patients with confirmed infections in waves 2 and 3 were younger and more likely to be residing in small cities and rural areas than were patients in wave 1; they also had a higher r ...201627191934
preliminary proteomic analysis of a549 cells infected with avian influenza virus h7n9 and influenza a virus h1n1.a newly emerged h7n9 influenza virus poses high risk to human beings. however, the pathogenic mechanism of the virus remains unclear. the temporal response of primary human alveolar adenocarcinoma epithelial cells (a549) infected with h7n9 influenza virus and h1n1 influenza a virus (h1n1, pdm09) were evaluated using the proteomics approaches (2d-dige combined with maldi-tof-ms/ms) at 24, 48 and 72 hours post of the infection (hpi). there were 11, 12 and 33 proteins with significant different exp ...201627223893
a new reassortment of influenza a (h7n9) virus causing human infection in beijing, 2014.a 73-year-old man was confirmed to have an influenza a (h7n9) virus infection, and the causative agent a/beijing/02/2014(h7n9) virus was isolated. genetic and phylogenetic analyses revealed that the virus belonged to a novel genotype, which probably emerged and further reassorted with other h9 or h7 viruses in poultry before transmitting to humans. this virus caused a severe infection with high levels of cytokines and neutralizing antibodies. eventually, the patient was cured after serially comb ...201627230107
epidemiological and virological differences in human clustered and sporadic infections with avian influenza a h7n9.previous research has suggested that avian influenza a h7n9 has a greater potential pandemic risk than influenza a h5n1. this research investigated the difference in human clustered and sporadic cases of h7n9 virus and estimated the relative risk of clustered infections.201627235087
limited transmission of emergent h7n9 influenza a virus in a simulated live animal market: do chickens pose the principal transmission threat?emergent h7n9 influenza a virus has caused multiple public health and financial hardships. while some epidemiological studies have recognized infected chickens as an important bridge for human infections, the generality of this observation, the minimum infectious dose, and the shedding potential of chickens have received conflicting results. we experimentally tested the ability of domestic chickens (gallus gallus domesticus) to transmit h7n9 to co-housed chickens and to several other animal spec ...201627236304
mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.immunomodulators have been shown to improve the outcome of severe pneumonia. we have previously shown that mycophenolic acid (mpa), an immunomodulator, has antiviral activity against influenza a/wsn/1933(h1n1) using a high-throughput chemical screening assay. this study further investigated the antiviral activity and mechanism of action of mpa against contemporary clinical isolates of influenza a and b viruses. the 50 % cellular cytotoxicity (cc50) of mpa in madin darby canine kidney cell line w ...201627259985
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
a novel small-molecule compound disrupts influenza a virus pb2 cap-binding and inhibits viral replication.the conserved residues 318-483 in the pb2 subunit of influenza a polymerase is an independently folded cap-binding domain (pb2cap) that exhibits a distinct binding mode from other host cap-binding proteins, which suggests that pb2cap might be an ideal drug target. this study aimed to identify a new class of anti-influenza inhibitors that specifically disrupts the interaction between pb2cap and host cap structures.201627272726
experimental challenge of a peridomestic avian species, european starlings ( sturnus vulgaris ), with novel influenza a h7n9 virus from china.in 2013 a novel avian influenza h7n9 virus was isolated from several critically ill patients in china, and infection with this virus has since caused more than 200 human deaths. live poultry markets are the likely locations of virus exposure to humans. peridomestic avian species also may play important roles in the transmission and maintenance of h7n9 at live poultry markets. we experimentally challenged wild european starlings ( sturnus vulgaris ) with the novel h7n9 virus and measured virus ex ...201627285413
[isolation and identification of a quail-origin h9n2 subtype of the influenza virus and its biologic characterization].a quail-origin subtype of the influenza virus was isolated from a human-infecting h7n9 subtype of the avian influenza virus found in a live poultry market and was given the name a/quail/hangzhou/1/ 2013 (h9n2). we analyzed the whole genome of this virus and its biologic characteristics. sequence analyses suggested that the: ha and ns genes belonged to a ck/bj/1/94-like lineage; na, np, pa and pb1 genes belonged to a sh/f/98-like lineage; m and pb2 genes belonged to a g1-like lineage. analyses of ...201627295886
rapid and sensitive detection of rna viruses based on reverse transcription loop-mediated isothermal amplification, magnetic nanoparticles, and chemiluminescence.rna viruses, particularly, the highly pathogenic avian influenza (hpai) virus, pose serious health concerns, and cause huge economic losses worldwide. diagnostic tools for the early detection of these deadly rna viruses are urgently needed to implement treatment and disease control strategies. conventional reverse transcription polymerase chain reaction (rt-pcr)-based chemiluminescent (rt-pcr-cl) detection is frequently used for the diagnosis of viral infections. however, the requirements for ex ...201627301197
detection of avian h7n9 influenza a viruses in the yangtze delta region of china during early h7n9 outbreaks.since the first h7n9 human case in shanghai, february 19, 2013, the emerging avian-origin h7n9 influenza a virus has become an epizootic virus in china, posing a potential pandemic threat to public health. from april 2 to april 28, 2013, some 422 oral-pharyngeal and cloacal swabs were collected from birds and environmental surfaces at five live poultry markets (lpms) and 13 backyard poultry farms (bpfs) across three cities, wuxi, suzhou, and nanjing, in the yangtze delta region. in total 22 isol ...201627309047
in vitro and in vivo attenuation of vesicular stomatitis virus (vsv) by phosphoprotein deletion.vesicular stomatitis virus (vsv) is highly immunogenic and able to stimulate both innate and adaptive immune responses. however, its ability to induce adverse effects has held back the use of vsv as a potential vaccine vector. in this study we developed vsv-δp, a safe yet potent replication-defective recombinant vsv in which the phosphoprotein (p) gene was deleted. vsv-δp replicated only in supporting cells expressing p (bhk-p cells) and at levels more than 2 logs lower than vsv. in vivo studies ...201627315286
antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir.favipiravir, a viral rna-dependent rna polymerase inhibitor, has recently been approved in japan for influenza pandemic preparedness. here, we conducted a cell-based screening system to evaluate the susceptibility of influenza viruses to favipiravir. in this assay, the antiviral activity of favipiravir is determined by inhibition of virus-induced cytopathic effect, which can be measured by using a colorimetric cell proliferation assay. to demonstrate the robustness of the assay, we compared the ...201627321665
ecological niche modeling of risk factors for h7n9 human infection in china.china was attacked by a serious influenza a (h7n9) virus in 2013. the first human infection case was confirmed in shanghai city and soon spread across most of eastern china. using the methods of geographic information systems (gis) and ecological niche modeling (enm), this research quantitatively analyzed the relationships between the h7n9 occurrence and the main environmental factors, including meteorological variables, human population density, bird migratory routes, wetland distribution, and ...201627322296
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
intranasal administration of chitosan against influenza a (h7n9) virus infection in a mouse model.influenza virus evolves constantly in an unpredictable fashion, making it necessary to vaccinate people annually for effective prevention and control of influenza. in general, however, during the first wave of an influenza outbreak caused by a newly emerging virus strain, influenza morbidity and mortality have been observed to rise sharply due to the lack of a matching vaccine. this necessitates the exploration of novel intervention approaches, particularly those prophylactic or therapeutic agen ...201627353250
the s128n mutation combined with an additional potential n-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human h7n9 virus. 201627381217
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
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
expression of inflammation-related genes in the lung of balb/c mice response to h7n9 influenza a virus with different pathogenicity.h7n9 influenza a virus (iav)-infected human cases are increasing and reported over 200 mortalities since its first emergence in 2013. host inflammatory response contributes to the clearance of influenza virus; meanwhile, the induced "cytokine storm" also leads to pathological lesions. however, what inflammation-related response of the host for h7n9 influenza a virus infection to survival from injures of exuberant cytokine release is still obscure. in this research, expression pattern and histolo ...201627401907
immunobiological properties of influenza a (h7n9) hemagglutinin and neuraminidase proteins.recombinant vaccinia viruses harboring the complete hemagglutinin (ha) or neuraminidase (na) genes from the influenza a/anhui/1/2013 (h7n9) virus were constructed (rvac-h7 ha and rvac-n9 na viruses). the ha and na proteins were expressed in the cytoplasm and on the plasma membrane of thymidine-kinase-negative (tk(-)) cells infected with these recombinant viruses. only one form of the ha protein was expressed in infected tk(-) cells, with a molecular weight (mw) of 75 kda, but three forms were fo ...201627406044
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
ribavirin is effective against drug-resistant h7n9 influenza virus infections. 201627430950
development of an influenza a master virus for generating high-growth reassortants for a/anhui/1/2013(h7n9) vaccine production in qualified mdck cells.in 2013, the first case of human infection with an avian influenza a virus (h7n9) was reported in china, and the human infection with this virus has continued as of 2016. at the request of the who, we have successfully developed candidate reassortant vaccine virus using a/anhui/1/2013 and the high egg-growth master virus a/pr/8/1934. recent plans regarding influenza vaccine production include using cell-cultured systems in japan and several other countries. however, egg-based vaccine viruses are ...201627454606
pathogenesis and phylogenetic analyses of two avian influenza h7n1 viruses isolated from wild birds.the emergence of human infections with a novel h7n9 influenza strain has raised global concerns about a potential human pandemic. to further understand the character of other influenza viruses of the h7 subtype, we selected two h7n1 avian influenza viruses (aivs) isolated from wild birds during routine surveillance in china: a/baer's pochard/hunan/414/2010 (bp/hun/414/10) (h7n1) and a/common pochard/xianghai/420/2010 (cp/xh/420/10) (h7n1). to better understand the molecular characteristics of th ...201627458455
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
sustained live poultry market surveillance contributes to early warnings for human infection with avian influenza viruses.sporadic human infections with the highly pathogenic avian influenza (hpai) a (h5n6) virus have been reported in different provinces in china since april 2014. from june 2015 to january 2016, routine live poultry market (lpm) surveillance was conducted in shenzhen, guangdong province. h5n6 viruses were not detected until november 2015. the h5n6 virus-positive rate increased markedly beginning in december 2015, and viruses were detected in lpms in all districts of the city. coincidently, two huma ...201627485495
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
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
chicken interferome: avian interferon-stimulated genes identified by microarray and rna-seq of primary chick embryo fibroblasts treated with a chicken type i interferon (ifn-α).viruses that infect birds pose major threats-to the global supply of chicken, the major, universally-acceptable meat, and as zoonotic agents (e.g. avian influenza viruses h5n1 and h7n9). controlling these viruses in birds as well as understanding their emergence into, and transmission amongst, humans will require considerable ingenuity and understanding of how different species defend themselves. the type i interferon-coordinated response constitutes the major antiviral innate defence. although ...201627494935
dual-component gene detection for h7n9 virus - the combination of optical trapping and bead-based fluorescence assay.we present a strategy of dual-component gene detection for avian influenza a virus h7n9 by combining optical trapping and bead-based fluorescence bioassays. a low-cost 473nm continuous dpss laser, polystyrene (ps) beads with two different sizes (3µm and 5µm in diameter) and streptavidin-modified 605nm quantum dots (sa-qds) were exploited in this platform. the beads were employed to enrich the targets using the classic sandwich mode and tagged with the sa-qds, then the qds-tagged beads floating i ...201627498332
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
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
cytokines and chemokines in mild/asymptomatic cases infected with avian influenza a (h7n9) virus. 201627534748
human mucosal-associated invariant t cells contribute to antiviral influenza immunity via il-18-dependent activation.mucosal-associated invariant t (mait) cells are innate-like t lymphocytes known to elicit potent immunity to a broad range of bacteria, mainly via the rapid production of inflammatory cytokines. whether mait cells contribute to antiviral immunity is less clear. here we asked whether mait cells produce cytokines/chemokines during severe human influenza virus infection. our analysis in patients hospitalized with avian h7n9 influenza pneumonia showed that individuals who recovered had higher number ...201627543331
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
long-term follow-up of 5 survivors after the first outbreak of human infections with avian influenza a(h7n9) virus in shanghai, china. 201627569243
economic burden and its associated factors of hospitalized patients infected with a (h7n9) virus: a retrospective study in eastern china, 2013-2014.h7n9 continues to cause human infections and remains a pandemic concern. understanding the economic impacts of this novel disease is important for making decisions on health resource allocation, including infectious disease prevention and control investment. however, there are limited data on such impacts.201627580946
isolation of h5n6, h7n9 and h9n2 avian influenza a viruses from air sampled at live poultry markets in china, 2014 and 2015.zoonotic infections by avian influenza viruses occur at the human-poultry interface, but the modes of transmission have not been fully investigated. we assessed the potential for airborne and fomite transmission at live poultry markets in guangzhou city and in hong kong special administrative region (sar), china, during 2014 and 2015. viral genome and infectious avian influenza a viruses of h5n6, h7n9, and h9n2 subtypes were detected predominantly from particles larger or equal to 1 μm in diamet ...201627608369
immunogenicity and safety of an as03-adjuvanted h7n9 pandemic influenza vaccine in a randomized trial in healthy adults.almost 700 cases of human infection with avian influenza a/h7n9 have been reported since 2013. pandemic preparedness strategies include h7n9 vaccine development.201627609809
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
genetic diversity and pathogenic potential of low pathogenic h7 avian influenza viruses isolated from wild migratory birds in korea.to detect the circulation of h7 avian influenza viruses, we characterized h7 viruses found in migratory birds and live poultry markets of south korea from 2005 to 2014. phylogenic analysis revealed that while all viruses clustered into the eurasian-lineage of h7 avian viruses, at least 12 distinct genotypes were represented. most h7 viruses contained at least one gene segment from the highly-pathogenic a/sck/hong kong/yu100/02(h5n1)-like avian virus, and they could be separated into at least two ...201627615552
coated protein nanoclusters from influenza h7n9 ha are highly immunogenic and induce robust protective immunity.recurring influenza viruses pose an annual threat to public health. a time-saving, cost-effective and egg-independent influenza vaccine approach is important particularly when responding to an emerging pandemic. we fabricated coated, two-layer protein nanoclusters from recombinant trimeric hemagglutinin from an avian-origin h7n9 influenza a virus as an approach for vaccine development in response to an emerging pandemic. assessment of the virus-specific immune responses and protective efficacy i ...201727622321
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
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
direct quantitative screening of influenza a virus without dna amplification by single-particle dual-mode total internal reflection scattering.quantitative screening of influenza a (h7n9) virus without dna amplification was performed based on single-particle dual-mode total internal reflection scattering (sd-tirs) with a transmission grating (tg). a gold nanopad was utilized as a substrate for the hybridization of probe dna molecules with the tirs nanotag (silver-nanoparticle). the tg effectively isolated the scattering signals in first-order spectral images (n=+1) of the nanotag from that of the substrate, providing excellent enhancem ...201727657846
immune repertoire diversity correlated with mortality in avian influenza a (h7n9) virus infected patients.specific changes in immune repertoires at genetic level responding to the lethal h7n9 virus are still poorly understood. we performed deep sequencing on the t and b cells from patients recently infected with h7n9 to explore the correlation between clinical outcomes and immune repertoire alterations. t and b cell repertoires display highly dynamic yet distinct clonotype alterations. during infection, t cell beta chain repertoire continues to contract while the diversity of immunoglobulin heavy ch ...201627669665
avian influenza a(h7n9) and (h5n1) infections among poultry and swine workers and the general population in beijing, china, 2013-2015.although several studies have reported seroprevalences of antibody against avian influenza a(h7n9) virus among poultry workers in southern china, results have varied and data in northern china are scarce. to understand risks of h7n9 and h5n1 virus infections in northern china, a serological cohort study was conducted. poultry workers, swine workers and the general population in beijing, china, were evaluated through three surveys in november 2013, april 2014 and april 2015. the highest seropreva ...201627670286
human-animal interface: the case for influenza interspecies transmission.since the 1990s, the threat of influenza viruses to veterinary and human public health has increased. this coincides with the larger global populations of poultry, pigs, and people and with changing ecological factors. these factors include the redistribution of the human population to cities, rapid mass transportation of people and infectious agents, increased global land use, climate change, and possible changes in viral ecology that perpetuate highly pathogenic influenza viruses in the aquati ...201627677275
quantitative risk analysis of the novel h7n9 virus in environments associated with h9 avian influenza virus, zhejiang province, china.h9 avian influenza virus played a key role during generation of the novel h7n9 virus. a surveillance programme was conducted to assess the h9 virus in relation to the risk of h7n9 virus contamination in the environment. risk of h7n9 virus contamination in the presence of h9 virus was higher than without (adjusted odds ratio 4·49, 95% confidence interval 3·79-5·31). adjusted odds ratios of the h7n9 virus associated with co-presence of h9 virus and interacting factors were 4·93 (rural vs. urban ar ...201727678396
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
susceptibility of chickens, quail, and pigeons to an h7n9 human influenza virus and subsequent egg-passaged strains.h7n9 human influenza virus a/anhui/1/2013 (anhui2013) showed low pathogenicity in chickens, quail, and pigeons, with quail being the most susceptible among the species tested. ivpie1-1, which was recovered from a dead chicken after intravenous inoculation of anhui 2013, had broader tissue tropism in chickens than did the original inoculum, as well as amino acid substitutions in the polymerase acidic gene and neuraminidase gene segments, but its pathogenicity was not enhanced. viruses obtained af ...201727686072
pharmacokinetics of intravenous peramivir in the airway epithelial lining fluid of healthy volunteers.some subtypes of influenza virus, such as h5n1 and h7n9, cause severe viral pneumonia, for which the intraluminal concentration of the anti-influenza agent in the airway is critical. however, the pharmacokinetics of peramivir, the only available injectable neuraminidase inhibitor formulation, in the airway epithelial lining fluid (elf) remains unclear. in this study, we aimed to determine the time course of peramivir in the pharyngeal elf, bronchial elf and plasma of healthy volunteers using bro ...201627694694
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
risk factors for influenza a(h7n9) disease in china, a matched case control study, october 2014 to april 2015.background.  human infections with avian influenza a(h7n9) virus have been associated with exposure to poultry and live poultry markets (lpms). we conducted a case-control study to identify additional and more specific risk factors. methods.  cases were laboratory-confirmed a(h7n9) infections in persons in china reported from october 1, 2014 to april 30, 2015. poultry workers, those with insufficient data, and those refusing participation were excluded. we matched up to 4 controls per case by se ...201627704029
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
an influenza a virus (h7n9) anti-neuraminidase monoclonal antibody with prophylactic and therapeutic activity in vivo.zoonotic a(h7n9) avian influenza viruses emerged in china in 2013 and continue to be a threat to human public health, having infected over 800 individuals with a mortality rate approaching 40%. treatment options for people infected with a(h7n9) include the use of neuraminidase (na) inhibitors. however, like other influenza viruses, a(h7n9) can become resistant to these drugs. the use of monoclonal antibodies is a rapidly developing strategy for controlling influenza virus infection. here we gene ...201627713074
role of r292k mutation in influenza h7n9 neuraminidase toward oseltamivir susceptibility: md and mm/pb(gb)sa study.the h7n9 avian influenza virus is a novel re-assortment from at least four different strains of virus. neuraminidase, which is a glycoprotein on the surface membrane, has been the target for drug treatment. however, some h7n9 strains that have been isolated from patient after drug treatment have a r292k mutation in neuraminidase. this substitution was found to facilitate drug resistance using protein- and virus- assays, in particular it gave a high resistance to the most commonly used drug, osel ...201627714494
factors associated with clinical outcome in 25 patients with avian influenza a (h7n9) infection in guangzhou, china.guangzhou reported its first laboratory-confirmed case of influenza a (h7n9) on january 10, 2014. a total of 25 cases were reported from the first wave of the epidemic until april 8, 2014. the fatality rate was much higher than in previous reports. the objective of the current work was to describe the clinical and epidemiological characteristics of a (h7n9) patients in guangzhou and explore possible reasons for the high fatality rate.201627716101
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
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
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
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
sero-epidemiologic study of influenza a(h7n9) infection among exposed populations, china 2013-2014.the first human infections of novel avian influenza a(h7n9) virus were identified in china in march 2013. sentinel surveillance systems and contact tracing may not identify mild and asymptomatic human infections of influenza a(h7n9) virus.201727762061
preclinical evaluation of the safety and pathogenicity of a live attenuated recombinant influenza a/h7n9 seed strain and corresponding mf59-adjuvanted split vaccine.developing a safe and effective h7n9 influenza vaccine was initiated in early spring 2013, following human infections with a novel avian influenza a (h7n9) virus. in this study, a candidate h7n9 vaccine seed strain is produced using reverse genetics, with ha and na derived from a human h7n9 virus and the remaining genes from the pr8 backbone virus which grows well in eggs. we verified that the virulence and transmissibility of the recombinant h7n9 vaccine seed strain were decreased as compared t ...201627768591
in vitro exposure system for study of aerosolized influenza virus.infection of adherent cell monolayers using a liquid inoculum represents an established method to reliably and quantitatively study virus infection, but poorly recapitulates the exposure and infection of cells in the respiratory tract that occurs during infection with aerosolized pathogens. to better simulate natural infection in vitro, we adapted a system that generates viral aerosols similar to those exhaled by infected humans to the inoculation of epithelial cell monolayers. procedures for ce ...201727771560
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
population seroprevalence of antibody to influenza a(h7n9) virus, guangzhou, china.since the identification in early 2013 of severe disease caused by influenza a(h7n9) virus infection, there have been few attempts to characterize the full severity profile of human infections. our objective was to estimate the number and severity of h7n9 infections in guangzhou, using a serological study.201627814756
fungal spondylodiscitis in a patient recovered from h7n9 virus infection: a case study and a literature review of the differences between candida and aspergillus spondylodiscitis.to report a rare case of fungal spondylodiscitis in a patient recovered from h7n9 virus infection and perform a literature review of the different characteristics of candida and aspergillus spondylodiscitis, we reviewed cases of spondylodiscitis caused by candida and aspergillus species. data, including patients' information, pathogenic species, treatment strategy, outcomes, and relapses, were collected and summarized. the characteristics of candida and aspergillus spondylodiscitis were compared ...201727819134
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
comparative studies of infectivity, immunogenicity and cross-protective efficacy of live attenuated influenza vaccines containing nucleoprotein from cold-adapted or wild-type influenza virus in a mouse model.this study sought to improve an existing live attenuated influenza vaccine (laiv) by including nucleoprotein (np) from wild-type virus rather than master donor virus (mdv). h7n9 laiv reassortants with 6:2 (np from mdv) and 5:3 (np from wild-type virus) genome compositions were compared with regard to their growth characteristics, induction of humoral and cellular immune responses in mice, and ability to protect mice against homologous and heterologous challenge viruses. although, in general, the ...201727829176
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
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
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
effect of live poultry market interventions on influenza a(h7n9) virus, guangdong, china.since march 2013, three waves of human infection with avian influenza a(h7n9) virus have been detected in china. to investigate virus transmission within and across epidemic waves, we used surveillance data and whole-genome analysis of viruses sampled in guangdong during 2013-2015. we observed a geographic shift of human a(h7n9) infections from the second to the third waves. live poultry market interventions were undertaken in epicenter cities; however, spatial phylogenetic analysis indicated th ...201627869613
nonlinear dynamics of avian influenza epidemic models.avian influenza is a zoonotic disease caused by the transmission of the avian influenza a virus, such as h5n1 and h7n9, from birds to humans. the avian influenza a h5n1 virus has caused more than 500 human infections worldwide with nearly a 60% death rate since it was first reported in hong kong in 1997. the four outbreaks of the avian influenza a h7n9 in china from march 2013 to june 2016 have resulted in 580 human cases including 202 deaths with a death rate of nearly 35%. in this paper, we co ...201727887851
pb2 substitutions v598t/i increase the virulence of h7n9 influenza a virus in mammals.pb2 is one of the subunits of the influenza a virus (iav) polymerase complex. by bioinformatics analysis we identified pb2 substitutions at positions 389 and 598 among iav isolates from humans, which might associate with viral pathogenicity. to evaluate the biological significance of these substitutions, pb2-k389r and -v598t/i mutant viruses of avian h7n9 iavs were generated by reverse genetics. compared to the wild type, the mutant viruses displayed an enhanced growth capacity in human and mamm ...201727889648
novel h7n2 and h5n6 avian influenza a viruses in sentinel chickens: a sentinel chicken surveillance study.in 2014, a sentinel chicken surveillance for avian influenza viruses was conducted in aquatic bird habitat near wuxi city, jiangsu province, china. two h7n2, one h5n6, and two h9n2 viruses were isolated. sequence analysis revealed that the h7n2 virus is a novel reassortant of h7n9 and h9n2 viruses and h5n6 virus is a reassortant of h5n1 clade 2.3.4 and h6n6 viruses. substitutions v186 and l226 (h3 numbering) in the hemagglutinin (ha) gene protein was found in two h7n2 viruses but not in the h5n6 ...201627899915
vaccination against h9n2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection.h9n2 avian influenza virus causes sporadic human infection. since humans do not possess acquired immunity specific to this virus, we examined the pathogenicity of an h9n2 virus isolated from a human and then analyzed protective effects of a vaccine in cynomolgus macaques. after intranasal challenge with a/hong kong/1073/1999 (h9n2) (hk1073) isolated from a human patient, viruses were isolated from nasal and tracheal swabs in unvaccinated macaques with mild fever and body weight loss. a formalin- ...201627910264
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
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
influenza virus-specific antibody dependent cellular cytoxicity induced by vaccination or natural infection.influenza viruses are responsible for substantial morbidity and mortality during seasonal epidemics. vaccination is the most effective method to prevent infection, however due to antigenic drift of the viral surface protein hemagglutinin (ha), annual influenza virus vaccination is required. in addition to seasonal viruses, certain (avian) influenza a viruses of other subtypes, like h5n1 or h7n9, cause sporadic zoonotic infections. therefore, the availability of game-changing novel vaccines that ...201727914742
genesis, evolution and prevalence of h5n6 avian influenza viruses in china.constant surveillance of live poultry markets (lpms) is currently the best way to predict and identify emerging avian influenza viruses (aivs) that pose a potential threat to public health. through surveillance of lpms from 16 provinces and municipalities in china during 2014-2016, we identified 3,174 aiv-positive samples and isolated and sequenced 1,135 aivs covering 31 subtypes. our analysis shows that h5n6 has replaced h5n1 as one of the dominant aiv subtypes in southern china, especially in ...201627916476
comparison of the first three waves of avian influenza a(h7n9) virus circulation in the mainland of the people's republic of china.h7n9 human cases were first detected in mainland china in march 2013. circulation of this virus has continued each year shifting to typical winter months. we compared the clinical and epidemiologic characteristics for the first three waves of virus circulation.201627919225
characterization of avian influenza a (h7n9) virus prevalence in humans and poultry in huai'an, china: molecular epidemiology, phylogenetic, and dynamics analyses.to trace the source of human h7n9 cases in huai'an and elucidate the genetic characterization of huai'an strains associated with both humans and birds in live poultry market.201627927274
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
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
assessing change in avian influenza a(h7n9) virus infections during the fourth epidemic - china, september 2015-august 2016.since human infections with avian influenza a(h7n9) virus were first reported by the chinese center for disease control and prevention (china cdc) in march 2013 (1), mainland china has experienced four influenza a(h7n9) virus epidemics. prior investigations demonstrated that age and sex distribution, clinical features, and exposure history of a(h7n9) virus human infections reported during the first three epidemics were similar (2). in this report, epidemiology and virology data from the most rec ...201627977644
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
structural basis of influenza virus fusion inhibition by the antiviral drug arbidol.the broad-spectrum antiviral drug arbidol shows efficacy against influenza viruses by targeting the hemagglutinin (ha) fusion machinery. however, the structural basis of the mechanism underlying fusion inhibition by arbidol has remained obscure, thereby hindering its further development as a specific and optimized influenza therapeutic. we determined crystal structures of arbidol in complex with influenza virus ha from pandemic 1968 h3n2 and recent 2013 h7n9 viruses. arbidol binds in a hydrophob ...201728003465
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
estimating risks of inapparent avian exposure for human infection: avian influenza virus a (h7n9) in zhejiang province, china.inapparent avian exposure was suspected for the sporadic infection of avian influenza a(h7n9) occurring in china. this type of exposure is usually unnoticed and difficult to model and measure. infected poultry with avian influenza h7n9 virus typically remains asymptomatic, which may facilitate infection through inapparent poultry/bird exposure, especially in a country with widespread practice of backyard poultry. the present study proposed a novel approach that integrated ecological and case-con ...201728054599
[research on spatiotemporal spread of avian influenza a(h7n9) virus based on discrete geographic information].objective: to establish a dynamic spatiotemporal spread modes of influenza a (h7n9) virus by using discrete geographic information and explore the spatiotemporal transmission of the virus. methods: the gene sequences of h7n9 virus isolated from human in china, which were available from global initiative on sharing avian influenza data (gisaid), were used in alignment by using software bioedit 7.0. spatiotemporal spread model of h7n9 virus was established in a bayesian statistical framework by us ...201628057141
multi-antigen avian influenza a (h7n9) virus-like particles: particulate characterizations and immunogenicity evaluation in murine and avian models.human infection with avian influenza a virus (h7n9) was first reported in china in march 2013. since then, hundreds of cases have been confirmed showing severe symptoms with a high mortality rate. the virus was transmitted from avian species to humans and has spread to many neighboring areas, raising serious concerns over its pandemic potential. towards containing the disease, the goal of this study is to prepare a virus-like particle (vlp) that consists of hemagglutinin (ha), neuraminidase (na) ...201728061848
on the role of cd8(+) t cells in determining recovery time from influenza virus infection.myriad experiments have identified an important role for cd8(+) t cell response mechanisms in determining recovery from influenza a virus infection. animal models of influenza infection further implicate multiple elements of the immune response in defining the dynamical characteristics of viral infection. to date, influenza virus models, while capturing particular aspects of the natural infection history, have been unable to reproduce the full gamut of observed viral kinetic behavior in a single ...201628066421
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
single pa mutation as a high yield determinant of avian influenza vaccines.human infection with an avian influenza virus persists. to prepare for a potential outbreak of avian influenza, we constructed a candidate vaccine virus (cvv) containing hemagglutinin (ha) and neuraminidase (na) genes of a h5n1 virus and evaluated its antigenic stability after serial passaging in embryonated chicken eggs. the passaged cvv harbored the four amino acid mutations (r136k in pb2; e31k in pa; a172t in ha; and r80q in m2) without changing its antigenicity, compared with the parental cv ...201728084423
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