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construction high-yield candidate influenza vaccine viruses in vero cells by reassortment.usage of influenza vaccine is the best choice measure for preventing and conclusion of influenza virus infection. although it has been used of chicken embryo to produce influenza vaccine, following with who recommended vaccine strain, there were uncontrollable factors and its deficiencies, specially, during an influenza pandemic in the world. the vero cells are used for vaccine production of a few strains including influenza virus, because of its homology with human, recommended by who. however, ...201627101353
comparison of pathogenicities of h7 avian influenza viruses via intranasal and conjunctival inoculation in cynomolgus macaques.the outbreak of h7n9 low pathogenic avian influenza viruses in china has attracted attention to h7 influenza virus infection in humans. since we have shown that the pathogenicity of h1n1 and h5n1 influenza viruses in macaques was almost the same as that in humans, we compared the pathogenicities of h7 avian influenza viruses in cynomolgus macaques via intranasal and conjunctival inoculation, which mimics natural infection in humans. h7n9 virus, as well as h7n7 highly pathogenic avian influenza v ...201626994587
human h7n9 virus induces a more pronounced pro-inflammatory cytokine but an attenuated interferon response in human bronchial epithelial cells when compared with an epidemiologically-linked chicken h7n9 virus.avian influenza virus h7n9 has jumped species barrier, causing sporadic human infections since 2013. we have previously isolated an h7n9 virus from a patient, and an h7n9 virus from a chicken in a live poultry market where the patient visited during the incubation period. these two viruses were genetically highly similar. this study sought to use a human bronchial epithelial cell line model to infer the virulence of these h7n9 viruses in humans.201626975414
a dna aptamer against influenza a virus: an effective inhibitor to the hemagglutinin-glycan interactions.most therapeutical nucleic acid aptamers tend to inhibit protein-protein interactions and thereby function as antagonists. attachment of the influenza virus surface glycoprotein hemagglutinin (ha) to sialic acid-containing host cell receptors (glycan) facilitates the initial stage of viral infection. inhibition of the attachment may result in an antiviral effect on the proliferation of the influenza virus. to develop therapeutically interesting agents, we selected two single-stranded dna (ssdna) ...201626904922
development of a high-yield reassortant influenza vaccine virus derived from the a/anhui/1/2013 (h7n9) strain.in april 2013, the first three fatal cases of human infection with an avian influenza a virus (h7n9) were reported in china. because of a pandemic threat by this virus, we have commenced to develop candidate vaccine viruses (cvvs). three 6:2 genetic reassortant viruses with different hemagglutinin (ha) sequences, niidrg-10, -10.1 and -10.2, were generated by a reverse genetics technique between the high egg-growth master virus, a/puerto rico/8/34 (h1n1) and a/anhui/1/2013 (h7n9), kindly provided ...201626657023
generation of a reassortant avian influenza virus h5n2 vaccine strain capable of protecting chickens against infection with egyptian h5n1 and h9n2 viruses.avian influenza h5n1 viruses have been enzootic in egyptian poultry since 2006. avian influenza h9n2 viruses which have been circulating in egyptian poultry since 2011 showed high replication rates in embryonated chicken eggs and mammalian cells.201626620838
type iii interferon gene expression in response to influenza virus infection in chicken and duck embryonic fibroblasts.type iii interferons (ifn-λs) comprise a group of newly identified antiviral cytokines that are functionally similar to type i ifns and elicit first-line antiviral responses. recently, type iii ifns were identified in several species; however, little information is available about type iii ifns in ducks. we compared the expression of type iii ifns and their receptor in chicken embryonic fibroblasts (cefs) and duck embryonic fibroblasts (defs) in response to influenza virus infection. the results ...201526598110
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
attenuation of the influenza virus by microrna response element in vivo and protective efficacy against 2009 pandemic h1n1 virus in mice.the 2009 influenza pandemics underscored the need for effective vaccines to block the spread of influenza virus infection. most live attenuated vaccines utilize cold-adapted, temperature-sensitive virus. an alternative to live attenuated virus is presented here, based on microrna-induced gene silencing.201526163223
host adaptation and the alteration of viral properties of the first influenza a/h1n1pdm09 virus isolated in japan.a/narita/1/2009 (a/n) was the first h1n1 virus from the 2009 pandemic (h1pdm) to be isolated in japan. to better understand and predict the possible development of this virus strain, the effect of passaging a/n was investigated in madin-darby canine kidney cells, chicken eggs and mice. a/n that had been continuously passaged in cells, eggs, or mice obtained the ability to grow efficiently in each host. moreover, a/n grown in mice had both a high level of pathogenicity in mice and an increased gr ...201526079133
the infection of turkeys and chickens by reassortants derived from pandemic h1n1 2009 and avian h9n2 influenza viruses.outbreaks of pandemic h1n1 2009 (ph1n1) in turkeys have been reported in several countries. co-infection of ph1n1 and avian h9n2 influenza viruses in turkeys provide the opportunity for their reassortment, and novel reassortant viruses might further be transmitted to other avian species. however, virulence and transmission of those reassortant viruses in poultry remain unclear. in the present study, we generated 16 single-gene reassortant influenza viruses including eight reassortants on the ph1 ...201526030097
identification of influenza a virus pb2 residues involved in enhanced polymerase activity and virus growth in mammalian cells at low temperatures.mutations in the polymerase genes are known to play a major role in avian influenza virus adaptation to mammalian hosts. despite having avian origin pa and pb2, the 2009 pandemic h1n1 virus (ph1n1) can replicate well in mammalian respiratory tracts, suggesting that these proteins have acquired mutations for efficient growth in humans. we have previously shown that pa from the ph1n1 virus a/california/04/09 (cal) strongly enhances activity of an otherwise avian polymerase complex derived from a/c ...201526018156
egg-adaptive mutations in h3n2v vaccine virus enhance egg-based production without loss of antigenicity or immunogenicity.the recently detected zoonotic h3n2 variant influenza a (h3n2v) viruses have caused 343 documented cases of human infection linked to contact with swine. an effective vaccine is needed for these viruses, which may acquire transmissibility among humans. however, viruses isolated from human cases do not replicate well in embryonated chicken eggs, posing an obstacle to egg-based vaccine production. to address this issue, we sought to identify egg-adaptive mutations in surface proteins that increase ...201525999284
specific inhibitory effect of κ-carrageenan polysaccharide on swine pandemic 2009 h1n1 influenza virus.the 2009 influenza a h1n1 pandemic placed unprecedented demands on antiviral drug resources and the vaccine industry. carrageenan, an extractive of red algae, has been proven to inhibit infection and multiplication of various enveloped viruses. the aim of this study was to examine the ability of κ-carrageenan to inhibit swine pandemic 2009 h1n1 influenza virus to gain an understanding of antiviral ability of κ-carrageenan. it was here demonstrated that κ-carrageenan had no cytotoxicity at concen ...201525969984
antiviral effects of novel herbal medicine kiom-c, on diverse viruses.in order to identify new potential antiviral agents, recent studies have advocated thorough testing of herbal medicines or natural substances that are traditionally used to prevent viral infections. antiviral activities and the mechanism of action of the total aqueous extract preparation of kiom-c, a novel herbal medicine, against diverse types of viruses were investigated. in vitro antiviral activity against a/puerto rico/8/34 (h1n1) (pr8), vesicular stomatitis virus (vsv), and newcastle diseas ...201525942440
intra-host viral variability in children clinically infected with h1n1 (2009) pandemic influenza.recent in-depth genetic analyses of influenza a virus samples have revealed patterns of intra-host viral genetic variability in a variety of relevant systems. these have included laboratory infected poultry, horses, pigs, chicken eggs and swine respiratory cells, as well as naturally infected poultry and horses. in humans, next generation sequencing techniques have enabled the study of genetic variability at specific positions of the viral genome. the present study investigated how 454 pyroseque ...201525891282
molecular responses to the influenza a virus in chicken trachea-derived cells.the influenza a virus infects a broad range of species and spreads easily through the respiratory tract. because of these characteristics, the influenza a virus has caused pandemic disease in humans and livestock. to investigate the early molecular responses after influenza a virus infection in chickens, we infected tracheal epithelial cells derived from 20-day-old chick embryos with influenza a virus (h1n1). the gene expression patterns of the infected tracheal epithelial cells were analyzed vi ...201525877411
[detection of the new influenza a subtype h1pdmn2 in a pig holding with severe respiratory symptoms].early in 2012 fattening pigs in a pig holding in northern baden-württemberg developed serious respiratory disease. after detecting influenza a specific rna by real time-rt-pcr in the lung of an euthanized pig, virus isolation was achieved in embryonated chicken eggs. the haemagglutination-inhibition (hi) test performed on this isolate showed a reaction with h1n1 specific serum, so the strain was initially characterised as subtype h1n1. however, serum samples from convalescent pigs of the same st ...201525876280
cell culture-based influenza vaccines: a necessary and indispensable investment for the future.the traditional platform of using embryonated chicken eggs for the production of influenza vaccines has several drawbacks including the inability to meet the volume of required doses in the case of widespread epidemics and pandemics. cell culture platforms have therefore been explored in the last 2 decades, and have attracted further attention following the h1n1 pandemic outbreak. this platform, while not the most economical for large-scale production, has several advantages, and can supplement ...201525875691
antiviral effect of methylated flavonol isorhamnetin against influenza.influenza is an infectious respiratory disease with frequent seasonal epidemics that causes a high rate of mortality and morbidity in humans, poultry, and animals. influenza is a serious economic concern due to the costly countermeasures it necessitates. in this study, we compared the antiviral activities of several flavonols and other flavonoids with similar, but distinct, hydroxyl or methyl substitution patterns at the 3, 3', and 4' positions of the 15-carbon flavonoid skeleton, and found that ...201525806943
14-deoxy-11,12-dehydroandrographolide exerts anti-influenza a virus activity and inhibits replication of h5n1 virus by restraining nuclear export of viral ribonucleoprotein complexes.the highly pathogenic avian influenza h5n1 virus has become a worldwide public health threat, and current antiviral therapies have limited activity against the emerging, resistant influenza viruses. therefore, effective drugs with novel targets against influenza a viruses, h5n1 strains in particular, should be developed. in the present study, 14-deoxy-11,12-dehydroandrographolide (dap), a major component of the traditional chinese medicine andrographis paniculata, exerted potent anti-influenza a ...201525800824
mammalian adaptive mutations of the pa protein of highly pathogenic avian h5n1 influenza virus.highly pathogenic h5n1 influenza a viruses continue to circulate among avian species and cause sporadic cases of human infection. therefore, the threat of a pandemic persists. however, the human cases of h5n1 infection have been limited mainly to individuals in close contact with infected poultry. these findings suggest that the h5n1 viruses need to acquire adaptive mutations to gain a replicative advantage in mammalian cells to break through the species barrier. many amino acid mutations of the ...201525631084
pa-x decreases the pathogenicity of highly pathogenic h5n1 influenza a virus in avian species by inhibiting virus replication and host response.pa-x is a newly discovered protein that decreases the virulence of the 1918 h1n1 virus in a mouse model. however, the role of pa-x in the pathogenesis of highly pathogenic avian influenza viruses (hpaiv) of the h5n1 subtype in avian species is totally unknown. by generating two pa-x-deficient viruses and evaluating their virulence in different animal models, we show here that pa-x diminishes the virulence of the hpaiv h5n1 strain a/chicken/jiangsu/k0402/2010 (ck10) in mice, chickens, and ducks. ...201525631083
influenza viruses with receptor-binding n1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice.in nearly all characterized influenza viruses, hemagglutinin (ha) is the receptor-binding protein while neuraminidase (na) is a receptor-cleaving protein that aids in viral release. however, in recent years, several groups have described point mutations that confer receptor-binding activity on na, albeit in laboratory rather than natural settings. one of these mutations, d151g, appears to arise in the na of recent human h3n2 viruses upon passage in tissue culture. we inadvertently isolated the s ...201525609803
chicken and duck myotubes are highly susceptible and permissive to influenza virus infection.skeletal muscle, at 30 to 40% of body mass, is the most abundant soft tissue in the body. besides its primary function in movement and posture, skeletal muscle is a significant innate immune organ with the capacity to produce cytokines and chemokines and respond to proinflammatory cytokines. little is known about the role of skeletal muscle during systemic influenza a virus infection in any host and particularly avian species. here we used primary chicken and duck multinucleated myotubes to exam ...201525540384
inhibition of reactive oxygen species production ameliorates inflammation induced by influenza a viruses via upregulation of socs1 and socs3.highly pathogenic avian influenza virus infection is associated with severe mortality in both humans and poultry. the mechanisms of disease pathogenesis and immunity are poorly understood although recent evidence suggests that cytokine/chemokine dysregulation contributes to disease severity following h5n1 infection. influenza a virus infection causes a rapid influx of inflammatory cells, resulting in increased reactive oxygen species production, cytokine expression, and acute lung injury. proinf ...201525520513
a vero-cell-adapted vaccine donor strain of influenza a virus generated by serial passages.a cell culture-based vaccine production system is preferred for the large-scale production of influenza vaccines and has advantages for generating vaccines against highly pathogenic influenza a viruses. vero cells have been widely used in human vaccine manufacturing, and the safety of these cells has been well demonstrated. however, the most commonly used influenza-vaccine donor virus, a/puerto rico/8/1934 (pr8) virus, does not grow efficiently in vero cells. therefore, we adapted the pr8 virus ...201525448099
protection of mice against pandemic h1n1 influenza virus challenge after immunization with baculovirus-expressed stabilizing peptide fusion hemagglutinin protein.current influenza vaccines are produced in embryonated chicken eggs. however, egg-based vaccines have various problems. to address these problems, recombinant protein vaccines have been developed as new vaccine candidates. unfortunately, recombinant proteins frequently encounter aggregation and low stability during their biogenesis. it has been previously demonstrated that recombinantly expressed proteins can be greatly stabilized with high solubility by fusing stabilizing peptide (sp) derived f ...201525394603
antibody response to dna vaccine against h5n1 avian influenza virus in broilers immunized according to three schedules.broiler type chickens were immunized intramuscularly with a dna vaccine encoding hemagglutinin (ha) from h5n1 avian influenza virus. the chickens were divided into four groups: control group which was not immunized, a group which obtained only one dose, and two groups which were immunized twice, one group with a boost two weeks after the priming and the other four weeks. blood samples were collected at several time points and the dynamics of the humoral response to the vaccine was studied. high ...201425180224
genetic characterization and evolution of h1n1pdm09 after circulation in a swine farm.following the emergence of the a(h1n1)pdm09 in humans, this novel influenza virus was reverse transmitted from infected people to swine population worldwide. in this study we investigated the molecular evolution of a(h1n1)pdm09 virus identified in pigs reared in a single herd. nasal swabs taken from pigs showing respiratory distress were tested for influenza type a and a(h1n1)pdm09 by real-time rt-pcr assays. virus isolation from positive samples was attempted by inoculation of nasal swabs sampl ...201425025062
apoptosis and pro-inflammatory cytokine response of mast cells induced by influenza a viruses.the pathogenesis of the influenza a virus has been investigated heavily, and both the inflammatory response and apoptosis have been found to have a definitive role in this process. the results of studies performed by the present and other groups have indicated that mast cells may play a role in the severity of the disease. to further investigate cellular responses to influenza a virus infection, apoptosis and inflammatory response were studied in mouse mastocytoma cell line p815. this is the fir ...201424923273
recombinant influenza h1, h5 and h9 hemagglutinins containing replaced h3 hemagglutinin transmembrane domain showed enhanced heterosubtypic protection in mice.influenza a viruses cause annual epidemics and irregular pandemics. a vaccine with heterosubtypic protection (hetero-protection) has been needed. in the present study, various influenza h1, h3, h5, and h9 hemagglutinin (ha) proteins were expressed in insect cells, and then mice were subcutaneously immunized with the expressed ha proteins, and challenged by influenza a viruses (a/puerto rico/8/1934 (h1n1) or a/chicken/guangdong/96 (h9n2)). the results first showed that wild-type h3 hemagglutinin ...201424704333
shortening the unstructured, interdomain region of the non-structural protein ns1 of an avian h1n1 influenza virus increases its replication and pathogenicity in chickens.currently circulating h5n1 influenza viruses have undergone a complex evolution since the appearance of their progenitor a/goose/guangdong/1/96 in 1996. after the eradication of the h5n1 viruses that emerged in hong kong in 1997 (hk/97 viruses), new genotypes of h5n1 viruses emerged in the same region in 2000 that were more pathogenic for both chickens and mice than hk/97 viruses. these, as well as virtually all highly pathogenic h5n1 viruses since 2000, harbour a deletion of aa 80-84 in the uns ...201424694396
changes in the ns1 gene of avian influenza viruses isolated in thailand affect expression of type i interferon in primary chicken embryonic fibroblast cells.the non-structural protein 1 (ns1) of avian influenza virus was defined as one of the virulent factors. to understand the effect of ns1 protein of influenza virus h5n1 isolated in thailand on type i (α/β) interferon (ifn) synthesis, five reverse genetic viruses were constructed and used as models. the viruses were generated using ns genomic segment from a/peurto rico/8/1934 (h1n1) and four avian influenza viruses isolated from the first outbreak in thailand. all the viruses have the rest of the ...201324426299
[engineering by reverse genetics and characterization of the new reassortant influenza virus strain h5n1].reverse genetics was applied to engineering of the reassortantvaccine candidate strain against highly pathogenic avian influenza viruses (hpaivs) of the h5 subtype. the new strain recpr8-h5n1 contains the ha gene from the russian hpaiv a/kurgan/05/2005 (h5n1), the na and internal genes from a/puerto rico/8/34 (h1n1). the strain recpr8-h5n1 demonstrated the antigenic specificity (h5), high proliferation rate in 12 days chicken embryos, and was lethal for the embryos in 36 hours. an inactivated em ...201425929032
egg- or cell culture-derived hemagglutinin mutations impair virus stability and antigen content of inactivated influenza vaccines.egg-derived viruses are the only available seed material for influenza vaccine production. vaccine manufacturing is done in embryonated chicken eggs, mdck or vero cells. in order to contribute to efficient production of influenza vaccines, we investigate whether the quality of inactivated vaccines is influenced by the propagation substrate. we demonstrate that h3n2 egg-derived seed viruses (a/brisbane/10/07, ivr147, and a/uruguay/716/07) triggered the hemagglutinin (ha) conformational change und ...201424323790
effects of different polymerases of avian influenza viruses on the growth and pathogenicity of a/puerto rico/8/1934 (h1n1)-derived reassorted viruses.we generated reassorted pr8 viruses containing six different combinations of avian influenza virus (aiv) polymerase genes from a/chicken/korea/01310/2001 (h9n2) (01310) and a/chicken/korea/kbnp-0028/2000 (h9n2) (0028) to examine the effects of the aiv polymerase genes pb1, pb2, and pa on replication efficiency in different host cells and pathogenicity in mice. the virus titers of the reassorted viruses possessing 01310 [rpr8-pb2(01310)] and 0028 [rpr8-pb2(0028)] pb2 genes were significantly high ...201424296300
anti-influenza activity of alchemilla mollis extract: possible virucidal activity against influenza virus particles.influenza virus infection is a major public health problem that leads to significant morbidity and mortality. the emergence of resistance to the currently available anti-influenza agents has necessitated the development of new drugs with novel targets. studying known ethno-medicinal plants is a promising approach for the discovery of new antiviral compounds. alchemilla mollis is used in traditional medicine in europe for different indications, including minimizing the symptoms of a sore throat. ...201324270383
new small molecule entry inhibitors targeting hemagglutinin-mediated influenza a virus fusion.influenza viruses are a major public health threat worldwide, and options for antiviral therapy are limited by the emergence of drug-resistant virus strains. the influenza virus glycoprotein hemagglutinin (ha) plays critical roles in the early stage of virus infection, including receptor binding and membrane fusion, making it a potential target for the development of anti-influenza drugs. using pseudotype virus-based high-throughput screens, we have identified several new small molecules capable ...201424198411
adjuvant efficacy of momv against avian influenza virus infection in mice.highly pathogenic avian influenza h5n1 viruses are found chiefly in birds and have caused severe disease and death in infected humans. development of influenza vaccines capable of inducing heterosubtypic immunity against a broad range of influenza viruses is the best option for the preparedness, since vaccination remains the principal method in controlling influenza viral infections. here, a momv-adjuvanted recombinant h5n2 (rh5n2) whole virus antigen vaccine with a/environment/korea/w149/06(h5n ...201324173647
an na-deficient 2009 pandemic h1n1 influenza virus mutant can efficiently replicate in cultured cells.we identified a novel neuraminidase (na)-deficient virus that was a 2009 pandemic influenza h1n1 virus mutant. the mutant virus had a deletion of 1,009 nt in the na gene and lacked an enzymatic domain. although the yield of the na-deficient virus was limited, it formed large plaques when applied to mdck cell cultures, indicating that the virus was able to spread to adjacent cells. furthermore, the na-deficient virus was eluted from chicken erythrocytes at 37 °c, even in the presence of the antiv ...201424142272
detection and isolation of influenza a virus subtype h1n1 from a small backyard swine herd in colorado.influenza a virus subtype h1n1 a(h1n1)pdm09 was first confirmed in pigs in the united states in october 2009. in november 2010, lungs and intestines from 2 york piglets from a small, privately owned herd were submitted to the colorado state university veterinary diagnostic laboratory. the submitting veterinarian reported rapid weight loss and signs of pneumonia in the piglets. gross lesions included caudoventral pneumonia in both piglets, and histologic lesions in the lungs showed characteristic ...201324081929
highly pathogenic avian influenza virus nucleoprotein interacts with trex complex adaptor protein aly/ref.we constructed a novel chicken (gallus gallus) lung cdna library fused inside yeast acting domain vector (pgadt7). using yeast two-hybrid screening with highly pathogenic avian influenza (hpai) nucleoprotein (np) from the strain (a/chicken/malaysia/5858/2004(h5n1)) as bait, and the gallus gallus lung cdna library as prey, a novel interaction between the gallus gallus cellular rna export adaptor protein aly/ref and the viral np was identified. this interaction was confirmed and validated with mam ...201324073193
full genome sequence of a natural reassortant h9n2 avian influenza virus isolated from domestic ducks in jiangsu province, china.in this study, the complete genomic sequence of a novel reassortant h9n2 avian influenza virus (aiv) from domestic ducks in eastern china was reported. phylogenetic analysis showed that seven of the eight genes were all highly homologous to the chicken-origin h9n2 viruses, whereas the pb2 gene was homologous to the human-origin h1n1 virus, which suggested that domestic ducks might play a key role in the genetic reassortment and evolution of h9n2 aivs in eastern china.201323868123
the short stalk length of highly pathogenic avian influenza h5n1 virus neuraminidase limits transmission of pandemic h1n1 virus in ferrets.h5n1 influenza viruses pose a pandemic threat but have not acquired the ability to support sustained transmission between mammals in nature. the restrictions to transmissibility of avian influenza viruses in mammals are multigenic, and overcoming them requires adaptations in hemagglutinin (ha) and pb2 genes. here we propose that a further restriction to mammalian transmission of the majority of highly pathogenic avian influenza (hpai) h5n1 viruses may be the short stalk length of the neuraminida ...201323864615
aptamers that bind to the hemagglutinin of the recent pandemic influenza virus h1n1 and efficiently inhibit agglutination.influenza virus hemagglutinin (ha) mediates both receptor (glycan) binding and membrane fusion for cell entry and has been the basis for typing influenza a viruses. in this study we have selected rna aptamers (d-12 and d-26) that specifically target the ha protein of the recent pandemic influenza virus pdmh1n1 (a/california/07/2009). among the selected aptamers the d-26 aptamer showed higher affinity for the ha of pdmh1n1 and was able to distinguish ha derived from other sub-types of influenza a ...201323791676
immunogenicity and protective efficacy of cold-adapted x-31 live attenuated pre-pandemic h5n1 influenza vaccines.despite global efforts to control influenza viruses, they have taken a heavy toll on human public health worldwide. among particular threats is highly pathogenic avian h5n1 influenza virus (hpai) due to not only its high mortality in humans but also possible human-to-human transmission either through reassortment with other human influenza viruses such as 2009 pandemic h1n1 influenza virus, or by genetic mutations. with the aim of developing effective vaccines against the h5n1 viruses, we genera ...201323742997
[design of deoxyribozymes for inhibition of influenza a virus].influenza a viruses take a significant place in human and animal pathology causing epidemics and epizootics. therefore, the development of new antiflu drugs has become more and more urgent. deoxyribozymes can be considered as promising antiviral agents due to their ability to efficiently and highly specifically cleave rna molecules. in this study, a number ofgenomic sequences of the most relevant influenza a virus subtypes, h5n1, h3n2, and h1n1, were analyzed. conservative regions were revealed ...201323705497
pandemic h1n1 influenza isolated from free-ranging northern elephant seals in 2010 off the central california coast.interspecies transmission of influenza a is an important factor in the evolution and ecology of influenza viruses. marine mammals are in contact with a number of influenza reservoirs, including aquatic birds and humans, and this may facilitate transmission among avian and mammalian hosts. virus isolation, whole genome sequencing, and hemagluttination inhibition assay confirmed that exposure to pandemic h1n1 influenza virus occurred among free-ranging northern elephant seals (mirounga angustirost ...201323690933
swine, human or avian influenza viruses differentially activates porcine dendritic cells cytokine profile.swine influenza virus (swiv) is considered a zoonosis and the fact that swine may act as an intermediate reservoir for avian influenza virus, potentially infectious for humans, highlights its relevance and the need to understand the interaction of different influenza viruses with the porcine immune system. thus, in vitro porcine bone marrow-derived dendritic cell (pobmdcs) were infected with a circulating swiv a/swine/spain/sf32071/2007(h3n2), 2009 human pandemic influenza virus a/catalonia/63/2 ...201323689011
glycosylation on hemagglutinin affects the virulence and pathogenicity of pandemic h1n1/2009 influenza a virus in mice.the two glycosylation sites (asn142 and asn177) were observed in the ha of most human seasonal influenza a/h1n1 viruses, while none in pandemic h1n1/2009 influenza a (ph1n1) viruses. we investigated the effect of the two glycosylation sites on viral virulence and pathogenicity in mice using recombinant ph1n1. the h1n1/144 and h1n1/177 mutants which gained potential glycosylation sites asn142 and asn177 on ha respectively were generated from a/mexico/4486/2009(h1n1) by site-directed mutagenesis a ...201323637827
antiviral activity of stachyflin on influenza a viruses of different hemagglutinin subtypes.the hemagglutinin (ha) of influenza viruses is a possible target for antiviral drugs because of its key roles in the initiation of infection. although it was found that a natural compound, stachyflin, inhibited the growth of h1 and h2 but not h3 influenza viruses in mdck cells, inhibitory activity of the compound has not been assessed against h4-h16 influenza viruses and the precise mechanism of inhibition has not been clarified.201323587221
potency under pressure: the impact of hydrostatic pressure on antigenic properties of influenza virus hemagglutinin.influenza vaccines are effective in protecting against illness and death caused by this seasonal pathogen. the potency of influenza vaccines is measured by single radial immunodiffusion (srid) assay that quantifies antigenic forms of hemagglutinin (ha). hydrostatic pressure results in loss of binding of influenza virus to red blood cells, but it is not known whether this infers loss of potency.201323496824
potency of a vaccine prepared from a/swine/hokkaido/2/1981 (h1n1) against a/narita/1/2009 (h1n1) pandemic influenza virus strain.the pandemic 2009 (h1n1) influenza virus has spread throughout the world and is now causing seasonal influenza. to prepare for the emergence of pandemic influenza, we have established a library of virus strains isolated from birds, pigs, and humans in global surveillance studies.201323384324
na proteins of influenza a viruses h1n1/2009, h5n1, and h9n2 show differential effects on infection initiation, virus release, and cell-cell fusion.two surface glycoproteins of influenza virus, haemagglutinin (ha) and neuraminidase (na), play opposite roles in terms of their interaction with host sialic acid receptors. ha attaches to sialic acid on host cell surface receptors to initiate virus infection while na removes these sialic acids to facilitate release of progeny virions. this functional opposition requires a balance. to explore what might happen when na of an influenza virus was replaced by one from another isolate or subtype, in t ...201323349854
prior infection of chickens with h1n1 or h1n2 avian influenza elicits partial heterologous protection against highly pathogenic h5n1.there is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. using chickens we have explored the possibility of using live low pathogenic avian influenza (lpai) a/goose/ab/223/2005 h1n1 or a/wbs/mb/325/2006 h1n2 to induce immunity against heterologous highly pathogenic avian influenza (hpai) a/chicken/vietnam/14/2005 h5n1. h1n1 and h1n2 re ...201223240067
toward animal cell culture-based influenza vaccine design: viral hemagglutinin n-glycosylation markedly impacts immunogenicity.the glycoproteins hemagglutinin (ha) and neuraminidase are the major determinants of host range and tissue tropism of the influenza virus. ha is the most abundant protein in the virus particle membrane and represents the basis of most influenza vaccines. it has been reported that influenza virus ha n-glycosylation markedly depends on the host cell line used for virus production. however, little is known about how differential glycosylation affects immunogenicity of the viral proteins. this is of ...201323225881
live attenuated influenza viruses produced in a suspension process with avian age1.cr.pix cells.current influenza vaccines are trivalent or quadrivalent inactivated split or subunit vaccines administered intramuscularly, or live attenuated influenza vaccines (laiv) adapted to replicate at temperatures below body temperature and administered intranasally. both vaccines are considered safe and efficient, but due to differences in specific properties may complement each other to ensure reliable vaccine coverage. by now, licensed laiv are produced in embryonated chicken eggs. in the near futur ...201223110398
prior infection of chickens with h1n1 avian influenza virus elicits heterologous protection against highly pathogenic h5n2.current vaccines for influenza are primarily killed whole virus vaccines that elicit antibody responses to the homologous virus but lack protection against heterologous viruses. using chickens as a model we have explored the possibility of using a live low pathogenic avian influenza (lpai) a/goose/ab/223/2005 h1n1 virus as a vaccine to generate protective immunity against heterologous highly pathogenic avian influenza (hpai) a/chicken/pensylvania/1370/1983 h5n2 virus challenge. virus replicated ...201223084852
isolation of the pandemic (h1n1) 2009 virus and its reassortant with an h3n2 swine influenza virus from healthy weaning pigs in thailand in 2011.a total of 300 nasal swabs were collected from 5 pig farms in two provinces in the eastern part of thailand in february 2011 and were subjected to viral isolation of influenza a viruses. two h3n2 and 6 h1n1 influenza a viruses were isolated from swabs collected from clinically healthy weaning pigs on farms in chonburi and chachoengsao provinces, respectively. the h3n2 isolates consisted of the hemagglutinin (ha) and neuraminidase (na) genes closely related to thai sivs and derived from a cluster ...201222906589
pathogenicity and transmissibility of reassortant h9 influenza viruses with genes from pandemic h1n1 virus.both h9n2 avian influenza and 2009 pandemic h1n1 viruses (ph1n1) are able to infect humans and swine, which has raised concerns that novel reassortant h9 viruses with ph1n1 genes might be generated in these hosts by reassortment. although previous studies have demonstrated that reassortant h9 viruses with ph1n1 genes show increased virulence in mice and transmissibility in ferrets, the virulence and transmissibility of reassortant h9 viruses in natural hosts such as chickens and swine remain unk ...201222875253
low pathogenicity avian influenza viruses infect chicken layers by different routes of inoculation.in order to develop better control measures against avian influenza, it is necessary to understand how the virus transmits in poultry. in a previous study in which the infectivity and transmissibility of the pandemic h1n1 influenza virus was examined in different poultry species, we found that no or minimal infection occurred in chicken and turkeys intranasally (in) inoculated with the virus. however, we demonstrated that the virus can infect laying turkey hens by the intracloacal (ic) and intra ...201222856182
heterologous interactions between ns1 proteins from different influenza a virus subtypes/strains.non-structural protein 1 (ns1) of the influenza virus plays a crucial role in modulating the host immune response and facilitating virus replication. the formation of a homodimer or an oligomer is necessary for ns1 to exert its function efficiently. in the present study, the ns1 protein from the a/shantou/602/06(h3n2) virus (herein abbreviated as ns32) was found to interact with ns1 from a/shantou/169/06(h1n1), a/chicken/guangdong/1/05(h5n1) and a/quail/hong kong/g1/97(h9n2) (abbreviated as ns11 ...201222744180
genetic engineering of live attenuated influenza viruses.the first live attenuated influenza vaccine (laiv) was licensed in the usa in 2003; it is a trivalent vaccine composed of two type a (h1n1 and h3n2) and one type b influenza virus each at 10(7) fluorescent focus units (ffu). each influenza vaccine strain is a reassortant virus that contains the hemagglutinin (ha) and neuraminidase (na) gene segments from a wild-type influenza virus and the six internal protein gene segments from a master donor virus (mdv) of either cold-adapted a/ann arbor/6/60 ...201222528159
tropism of pandemic 2009 h1n1 influenza a virus.substitutions at the receptor-binding site of the pandemic h1n1 2009 influenza a virus (h1n1pdm) hemagglutinin (ha) gene may be critical in determining whether a virus binds to human or avian receptors. previous reports suggest that ha gly(222) and/or arg(223) allow viruses to bind preferentially to the α2,3-linked sialic acid found in avian species. we also demonstrated that serial passaging of influenza a virus in embryonated chicken eggs increased viral growth 32- to 64-fold, coincident with ...201222493594
distribution patterns of influenza virus receptors and viral attachment patterns in the respiratory and intestinal tracts of seven avian species.this study assessed the presence of sialic acid α-2,3 and α-2,6 linked glycan receptors in seven avian species. the respiratory and intestinal tracts of the chicken, common quail, red-legged partridge, turkey, golden pheasant, ostrich, and mallard were tested by means of lectin histochemistry, using the lectins maackia amurensis agglutinin ii and sambucus nigra agglutinin, which show affinity for α-2,3 and α-2,6 receptors, respectively. additionally, the pattern of virus attachment (pva) was eva ...201222489675
improvement of influenza vaccine strain a/vietnam/1194/2004 (h5n1) growth with the neuraminidase packaging sequence from a/puerto rico/8/34.h5n1 influenza candidate vaccine viruses were developed using the "6+2" approach. the hemagglutinin (ha) and neuraminidase (na) genes were derived from the popular h5n1 virus and the remaining six internal segments were derived from the a/puerto rico/8/34 strain (h1n1, pr8). however, some of these candidate strains have been reported to produce relatively low yields in vaccine manufacture. in this study, we found that the na vrna of the a/vietnam/1194/2004 strain (h5n1, vn1194) was poorly packag ...201222426370
identification of dual receptor-binding specific strains of human h5n1 viruses in china.both the 2, 6 linkage and its topology on target cells are critical for the recognition by human influenza virus. the binding preference of avian flu virus h5n1 ha to the 2, 3-linked sialylated glycans is considered the major factor limiting its efficient infection and transmission in humans. to monitor potential adaptation of h5n1 virus in human population, the surveillance of receptor-binding specificity was undertaken in china.201222424634
interspecies interactions and potential influenza a virus risk in small swine farms in peru.the recent avian influenza epidemic in asia and the h1n1 pandemic demonstrated that influenza a viruses pose a threat to global public health. the animal origins of the viruses confirmed the potential for interspecies transmission. swine are hypothesized to be prime "mixing vessels" due to the dual receptivity of their trachea to human and avian strains. additionally, avian and human influenza viruses have previously been isolated in swine. therefore, understanding interspecies contact on smallh ...201222420542
regulatory, biosafety and safety challenges for novel cells as substrates for human vaccines.in the development of novel substrates used for production of human vaccines there has been significant progress made in recent years. emerging and re-emerging infectious diseases like the recent porcine influenza a virus (h1n1) pandemic necessitated the availability of unprecedented amounts of vaccines. in addition, the high demand for vaccines in the industrialised countries has also been paralleled by a steep increase in demand in developing countries. the manufacturing capability for viral v ...201222342707
mucosally administered lactobacillus surface-displayed influenza antigens (sm2 and ha2) with cholera toxin subunit a1 (cta1) induce broadly protective immune responses against divergent influenza subtypes.the development of a universal influenza vaccine that provides broad cross protection against existing and unforeseen influenza viruses is a critical challenge. in this study, we constructed and expressed conserved sm2 and ha2 influenza antigens with cholera toxin subunit a1 (cta1) on the surface of lactobacillus casei (pgsa-cta1sm2ha2/l. casei). oral and nasal administrations of recombinant l. casei into mice resulted in high levels of serum immunoglobulin g (igg) and their isotypes (igg1 & igg ...201526210951
mucosal vaccination with recombinant lactobacillus casei-displayed cta1-conjugated consensus matrix protein-2 (sm2) induces broad protection against divergent influenza subtypes in balb/c mice.to develop a safe and effective mucosal vaccine against pathogenic influenza viruses, we constructed recombinant lactobacillus casei strains that express conserved matrix protein 2 with (pgsa-cta1-sm2/l. casei) or without (pgsa-sm2/l. casei) cholera toxin subunit a1 (cta1) on the surface. the surface localization of the fusion protein was verified by cellular fractionation analyses, flow cytometry and immunofluorescence microscopy. oral and nasal inoculations of recombinant l. casei into mice re ...201424714362
mucosal vaccination of conserved sm2, ha2 and cholera toxin subunit a1 (cta1) fusion protein with poly gamma-glutamate/chitosan nanoparticles (pc nps) induces protection against divergent influenza subtypes.to develop a safe and effective mucosal vaccine that broad cross protection against seasonal or emerging influenza a viruses, we generated a mucosal influenza vaccine system combining the highly conserved matrix protein-2 (sm2), fusion peptide of hemagglutinin (ha2), the well-known mucosal adjuvant cholera toxin subunit a1 (cta1) and poly-γ-glutamic acid (γ-pga)-chitosan nanoparticles (pc nps), which are safe, natural materials that are able to target the mucosal membrane as a mucosal adjuvant. ...201728284616
influenza a viruses replicate productively in mouse mastocytoma cells (p815) and trigger pro-inflammatory cytokine and chemokine production through tlr3 signaling pathway.the influenza a viruses (iavs) cause acute respiratory infection in both humans and animals. as a member of the initial lines of host defense system, the role of mast cells during iav infection has been poorly understood. here, we characterized for the first time that both avian-like (α-2, 3-linked) and human-like (α-2, 6- linked) sialic acid (sa) receptors were expressed by the mouse mastocytoma cell line (p815). the p815 cells did support the productive replication of h1n1 (a/wsn/33), h5n1 (a/ ...201628127293
neu5acα2,6gal and neu5acα2,3gal receptor specificities on influenza viruses determined by a waveguide-mode sensor.to characterize the differences in the receptor-binding specificities of human and avian influenza viruses with glycan chains, the authors performed binding analyses using an evanescent field-coupled waveguide-mode biosensor. the experiments were performed on intact viruses and hemagglutinin proteins, using gold-nanoparticle-conjugated neu5acα2,6gal and neu5acα2,3gal glycan chains. several influenza viruses belonging to subtypes h3n2 (a/udorn/307/1972, a/shandong/9/1993, a/kiev/301/1994, a/panam ...201323022889
[anaphylactic reactions to vaccines : chicken egg allergy and the influenza h1n1 vaccination].allergic reactions to influenza vaccinations are a well-known phenomenon; however, only a few published statistics give information on the risks. patients with a chicken egg allergy must be particularly carefully handled during an influenza epidemic where vaccines produced using embryonated chicken eggs are primarily employed.201728540396
vaccination with killed but metabolically active e. coli over-expressing hemagglutinin elicits neutralizing antibodies to h1n1 swine origin influenza a virus.there is a need for a fast and simple method for vaccine production to keep up with the pace of a rapidly spreading virus in the early phases of the influenza pandemic. the use of whole viruses produced in chicken eggs or recombinant antigens purified from various expression systems has presented considerable challenges, especially with lengthy processing times. here, we use the killed but metabolically active (kbma) escherichia coli (e. coli) to harbor the hemagglutinin (ha) of swine origin inf ...201728492063
[evolution and infection biology of new influenza a viruses with pandemic potential].wild aquatic birds are natural hosts for a large variety of influenza a viruses. occasionally, viruses are transmitted from this reservoir to other species, such as chickens, pigs, and man, and may then cause devastating outbreaks in domestic poultry or give rise to human influenza pandemics. the h5n1-, h7n7-, h9n2-, and h2n2-viruses are considered to have high pandemic potential, because of their pathogenicity in humans and because of the lack of immune protection in the human population. howev ...201323275951
identification and characterization of influenza a viruses in selected domestic animals in kenya, 2010-2012.influenza a virus subtypes in non-human hosts have not been characterized in kenya. we carried out influenza surveillance in selected domestic animals and compared the virus isolates with isolates obtained in humans during the same period.201829425232
differential responses of innate immunity triggered by different subtypes of influenza a viruses in human and avian hosts.innate immunity provides first line of defense against viral infections. the interactions between hosts and influenza a virus and the response of host innate immunity to viral infection are critical determinants for the pathogenicity or virulence of influenza a viruses. this study was designed to investigate global changes of gene expression and detailed responses of innate immune systems in human and avian hosts during the course of infection with various subtypes of influenza a viruses, using ...201729322931
a y161f hemagglutinin substitution increases thermostability and improves yields of 2009 h1n1 influenza a virus in cells.vaccination is the primary strategy for influenza prevention and control. however, egg-based vaccines, the predominant production platform, have several disadvantages, including the emergence of viral antigenic variants that can be induced during egg passage. these limitations have prompted the development of cell-based vaccines, which themselves are not without issue. most importantly, vaccine seed viruses often do not grow efficiently in mammalian cell lines. here we aimed to identify novel hi ...201829118117
a two dose immunization with an inactivated reassortant h5n2 virus protects chickens against lethal challenge with homologous 2.3.2.1 clade and heterologous 2.2 clade highly pathogenic avian influenza h5n1 viruses.the present study was aimed at generating a reassortant vaccine candidate virus with clade 2.3.2.1 hemagglutinin (ha) and its evaluation in a challenge study for protection against homologous (2.3.2.1 clade) and heterologous (2.2 clade) highly pathogenic avian influenza (hpai) h5n1 viruses. plasmid-based reverse genetics technique was used to rescue a 5 + 3 reassortant h5n2 strain containing the modified ha of h5n1 (clade 2.3.2.1), the neuraminidase (na) of h9n2, the matrix (m) of h5n1 and the i ...201829615248
risk for interspecies transmission of zoonotic pathogens during poultry processing and pork production in peru: a qualitative study.interspecies transmission of pathogens is an unfrequent but naturally occurring event and human activities may favour opportunities not previously reported. reassortment of zoonotic pathogens like influenza a virus can result from these activities. recently, swine and birds have played a central role as "mixing vessels" for epidemic and pandemic events related to strains like h1n1 and h5n1. unsafe practices in poultry markets and swine farms can lead to interspecies transmission, favouring the e ...201829602269
comparative pathogenicity and transmissibility of pandemic h1n1, avian h5n1, and human h7n9 influenza viruses in tree shrews.influenza a viruses (iavs) continuously challenge the poultry industry and human health. studies of iavs are still hampered by the availability of suitable animal models. chinese tree shrews (tupaia belangeri chinensis) are closely related to primates physiologically and genetically, which make them a potential animal model for human diseases. in this study, we comprehensively evaluated infectivity and transmissibility in chinese tree shrews by using pandemic h1n1 (a/sichuan/1/2009, pdmh1n1), av ...201931921093
full-length genome sequences of the first h9n2 avian influenza viruses isolated in the northeast of algeria.h9n2 avian influenza viruses (aiv) has a worldwide geographic distribution and affects poultry of different types of production. h9n2 aiv was first reported in the northeast of algeria in april 2017, following an outbreak associated with high mortality, in broiler flocks. in the present study, we report full-length genome sequences of aiv h9n2, and the detailed phylogeny and molecular genetic analyses.202032680533
irradiation by a combination of different peak-wavelength ultraviolet-light emitting diodes enhances the inactivation of influenza a viruses.influenza a viruses (iavs) pose a serious global threat to humans and their livestock. this study aimed to determine the ideal irradiation by ultraviolet-light emitting diodes (uv-leds) for iav disinfection. we irradiated the iav h1n1 subtype with 4.8 mj/cm2 uv using eight uv-leds [peak wavelengths (wl) = 365, 310, 300, 290, 280, 270, and 260 nm)] or a mercury low pressure (lp)-uv lamp (peak wl = 254 nm). inactivation was evaluated by the infection ratio of madin-darby canine kidney (mdck) cells ...202032650492
an r195k mutation in the pa-x protein increases the virulence and transmission of influenza a virus in mammalian hosts.in the 21st century, the emergence of h7n9 and h1n1/2009 influenza viruses, originating from animals and causing severe human infections, has prompted investigations into the genetic alterations required for cross-species transmission. we previously found that replacement of the human-origin pa gene segment in avian influenza virus (aiv) could overcome barriers to cross-species transmission. recently, it was reported that the pa gene segment encodes both the pa protein and a second protein, pa-x ...202032161172
evolution of h5-type avian influenza a virus towards mammalian tropism in egypt, 2014 to 2015.highly pathogenic avian influenza viruses (hpaiv) of the h5-subtype have circulated continuously in egypt since 2006, resulting in numerous poultry outbreaks and considerable sporadic human infections. the extensive circulation and wide spread of these viruses in domestic poultry have resulted in various evolutionary changes with a dramatic impact on viral transmission ability to contact mammals including humans. the transmitted viruses are either (1) adapted well enough in their avian hosts to ...201931703251
biosafety risk assessment for production of candidate vaccine viruses to protect humans from zoonotic highly pathogenic avian influenza viruses.a major lesson learned from the public health response to the 2009 h1n1 pandemic was the need to shorten the vaccine delivery timeline to achieve the best pandemic mitigation results. a gap analysis of previous pre-pandemic vaccine development activities identified possible changes in the select agent exclusion process that would maintain safety and shorten the timeline to develop candidate vaccine viruses (cvvs) for use in pandemic vaccine manufacture. here, we review the biosafety characterist ...202031659871
genetic characteristics and polymorphisms in the chicken interferon-induced transmembrane protein (ifitm3) gene.the interferon-induced transmembrane protein 3 (ifitm3) gene is classified as a small interferon-stimulated gene and is associated with a broad spectrum of antiviral functions against several fatal enveloped viruses, including influenza a viruses (iavs). the rs12252 single nucleotide polymorphism (snp) of the ifitm3 gene in humans was associated with susceptibility to h1n1 influenza in a 2009 pandemic. in addition, overexpression of the ifitm3 protein potently inhibits the highly pathogenic avia ...201931410631
mutation of influenza a virus pa-x decreases pathogenicity in chicken embryos and can increase the yield of reassortant candidate vaccine viruses.the pa-x protein of influenza a virus has roles in host cell shutoff and viral pathogenesis. while most strains are predicted to encode pa-x, strain-dependent variations in activity have been noted. we found that pa-x protein from the a/pr/8/34 (pr8) strain had significantly lower repressive activity against cellular gene expression than pa-x proteins from the avian strains a/turkey/england/50-92/91 (h5n1) (t/e) and a/chicken/rostock/34 (h7n1). loss of normal pa-x expression, either by mutation ...201930381488
evaluation of the potential defensive strategy against influenza a in cell line models.background: influenza virus can cause both seasonal infections and unpredictable pandemics. rapidly evolving avian h5n1 and  h7n9 viruses have a potential pandemic threat for humans. since avian influenza can be transmitted by domestic birds, serving as a key link between wild birds and humans, an effective measure to control the influenza transmission would be eradication of the infection in poultry. it is known that the virus penetrates into the cell through binding with the terminal oligosacc ...201829946435
the second-generation thiazolide haloxanide is a potent inhibitor of avian influenza virus replication.the emergence of new avian influenza virus (aiv) strains able to infect humans represents a serious threat to global human health. in addition to surveillance and vaccine development, antiviral therapy remains crucial for aiv control; however, the increase in drug-resistant aiv strains underscores the need for novel approaches to anti-influenza chemotherapy. we have previously shown that the thiazolide anti-infective nitazoxanide (ntz) inhibits influenza a/puertorico/8/1934(h1n1) virus replicati ...201829908209
functional growth inhibition of influenza a and b viruses by liquid and powder components of leaves from the subtropical plant melia azedarach l.we evaluated the anti-influenza-virus effects of melia components and discuss the utility of these components. the effects of leaf components of melia azedarach l. on viruses were examined, and plaque inhibition tests were performed. the in vivo efficacy of m. azedarach l. was tested in a mouse model. leaf components of melia azedarach l. markedly inhibited the growth of various influenza viruses. in an initial screening, multiplication and haemagglutination (ha) activities of h1n1, h3n2, h5, an ...201829633076
ns segment of a 1918 influenza a virus-descendent enhances replication of h1n1pdm09 and virus-induced cellular immune response in mammalian and avian systems.the 2009 pandemic influenza a virus (iav) h1n1 strain (h1n1pdm09) has widely spread and is circulating in humans and swine together with other human and avian iavs. this fact raises the concern that reassortment between h1n1pdm09 and co-circulating viruses might lead to an increase of h1n1pdm09 pathogenicity in different susceptible host species. herein, we explored the potential of different ns segments to enhance the replication dynamics, pathogenicity and host range of h1n1pdm09 strain a/gies ...201829623073
14-deoxy-11,12-didehydroandrographolide inhibits apoptosis in influenza a(h5n1) virus-infected human lung epithelial cells via the caspase-9-dependent intrinsic apoptotic pathway which contributes to its antiviral activity.influenza a virus (iav) infection represents a global health challenge. excavating antiviral active components from traditional chinese medicine (tcm) is a promising anti-iav strategy. our previous studies have demonstrated that 14-deoxy-11,12-didehydroandrographolide (dap), a major ingredient of a tcm herb called andrographis paniculata, shows anti-iav activity that is mainly effective against a/chicken/hubei/327/2004 (h5n1), a/duck/hubei/xn/2007 (h5n1), and a/pr/8/34 (h1n1) in vitro and in viv ...202032702348
a77 1726, the active metabolite of the anti-rheumatoid arthritis drug leflunomide, inhibits influenza a virus replication in vitro and in vivo by inhibiting the activity of janus kinases.the newly reassorted iav subtypes from zoonotic reservoirs respond poorly to current vaccines and antiviral therapy. there is an unmet need in developing novel antiviral drugs for better control of iav infection. the cellular factors that are crucial for virus replication have been sought as novel molecular targets for antiviral therapy. recent studies have shown that janus kinases (jak), jak1, and jak2, play an important role in iav replication. leflunomide is an anti-inflammatory drug primaril ...202032598086
immune response and protective efficacy of inactivated and live influenza vaccines against homologous and heterosubtypic challenge.inactivated (whole-virion, split, subunit, and adjuvanted) vaccines and live attenuated vaccine were tested in parallel to compare their immunogenicity and protective efficacy. homologous and heterosubtypic protection against the challenge with influenza h5n1 and h1n1 viruses in a mouse model were studied. single immunization with live or inactivated whole-virion h5n1 vaccine elicited a high level of serum antibodies and provided complete protection against the challenge with the lethal a/chicke ...202032571185
inter-species host gene expression differences in response to human and avian influenza a virus strains.low pathogenic avian influenza (lpai) viruses are a source of sporadic human infections and could also contribute to future pandemic outbreaks but little is known about inter-species differences in the host responses to these viruses. here, we studied host gene expression signatures of cell lines from three species (human, chicken, and canine) in response to six different viruses (h1n1/wsn, h5n2/f59, h5n2/f118, h5n2/f189, h5n3 and h9n2). comprehensive microarray probe set re-annotation and ortho ...201729104227
antiviral activity of chicken cathelicidin b1 against influenza a virus.cathelicidins (caths) are host defense peptides (hdps) that play an important role in the innate immune response against infections. although multiple functions of cathelicidins have been described, including direct antimicrobial activity and several immunomodulatory effects on the host, relatively little is known about their antiviral activity. therefore, in vitro antiviral activity of chicken cathelicidins and the underlying mechanism was investigated in this study against different influenza ...202032265870
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