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substitutions t200a and e227a in the hemagglutinin of pandemic 2009 influenza a virus increase lethality but decrease transmission.we report that swine influenza virus-like substitutions t200a and e227a in the hemagglutinin (ha) of the 2009 pandemic influenza virus alter its pathogenesis and transmission. viral replication is increased in mammalian cells. infected mice show increased disease as measured by weight loss and lethality. transmission in ferrets is decreased in the presence of both substitutions, suggesting that amino acids 200t and 227e are adaptive changes in the ha of swine origin influenza viruses associated ...201323536663
isolation of a novel swine influenza virus from oklahoma in 2011 which is distantly related to human influenza c viruses.of the orthomyxoviridae family of viruses, only influenza a viruses are thought to exist as multiple subtypes and has non-human maintenance hosts. in april 2011, nasal swabs were collected for virus isolation from pigs exhibiting influenza-like illness. subsequent electron microscopic, biochemical, and genetic studies identified an orthomyxovirus with seven rna segments exhibiting approximately 50% overall amino acid identity to human influenza c virus. based on its genetic organizational simila ...201323408893
review of a new molecular virus pathotyping method in the context of bioterrorism.avian influenza virus (aiv) and newcastle disease virus (ndv) infect various avian species including domestic poultry. clinical manifestations vary from subclinical or mild to severe multiorgan systemic disease with a near 100% mortality rate. severe disease is caused by highly virulent specific virus strains, termed highly pathogenic aiv and velogenic ndv. recent controversial influenza h5 adaptation studies in ferrets have highlighted the importance of preparedness against aiv as a bioterroris ...201323971812
identification and structural characterization of a broadly neutralizing antibody targeting a novel conserved epitope on the influenza virus h5n1 hemagglutinin.the unabated circulation of the highly pathogenic avian influenza a virus/h5n1 continues to be a serious threat to public health worldwide. because of the high frequency of naturally occurring mutations, the emergence of h5n1 variants with high virulence has raised great concerns about the potential transmissibility of the virus in humans. recent studies have shown that laboratory-mutated or reassortant h5n1 viruses could be efficiently transmitted among mammals, particularly ferrets, the best a ...201323221567
an adenovirus-based vaccine with a double-stranded rna adjuvant protects mice and ferrets against h5n1 avian influenza in oral delivery models.an oral gene-based avian influenza vaccine would allow rapid development and simplified distribution, but efficacy has previously been difficult to achieve by the oral route. this study assessed protection against avian influenza virus challenge using a chimeric adenovirus vector expressing hemagglutinin and a double-stranded rna adjuvant. immunized ferrets and mice were protected upon lethal challenge. further, ferrets immunized by the peroral route induced cross-clade neutralizing antibodies, ...201323155123
pathogenesis, transmissibility, and ocular tropism of a highly pathogenic avian influenza a (h7n3) virus associated with human conjunctivitis.h7 subtype influenza a viruses, responsible for numerous outbreaks in land-based poultry in europe and the americas, have caused over 100 cases of confirmed or presumed human infection over the last decade. the emergence of a highly pathogenic avian influenza h7n3 virus in poultry throughout the state of jalisco, mexico, resulting in two cases of human infection, prompted us to examine the virulence of this virus (a/mexico/indre7218/2012 [mx/7218]) and related avian h7 subtype viruses in mouse a ...201323487452
the mouse and ferret models for studying the novel avian-origin human influenza a (h7n9) virus.the current study was conducted to establish animal models (including mouse and ferret) for the novel avian-origin h7n9 influenza virus.201323927489
low pathogenic avian influenza a(h7n9) virus causes high mortality in ferrets upon intratracheal challenge: a model to study intervention strategies.infections with low pathogenic avian influenza (lpai) a(h7n9) viruses have caused more than 100 hospitalized human cases of severe influenza in china since february 2013 with a case fatality rate exceeding 25%. most of these human infections presented with severe viral pneumonia, while limited information is available currently on the occurrence of mild and subclinical cases. in the present study, a ferret model for this virus infection in humans is presented to evaluate the pathogenesis of the ...201323816392
quantitative characterization of glycan-receptor binding of h9n2 influenza a virus hemagglutinin.avian influenza subtypes such as h5, h7 and h9 are yet to adapt to the human host so as to establish airborne transmission between humans. however, lab-generated reassorted viruses possessing hemagglutinin (ha) and neuraminidase (na) genes from an avian h9 isolate and other genes from a human-adapted (h3 or h1) subtype acquired two amino acid changes in ha and a single amino acid change in na that confer respiratory droplet transmission in ferrets. we previously demonstrated for human-adapted h1 ...201323626667
metagenomic analysis of the ferret fecal viral flora.ferrets are widely used as a small animal model for a number of viral infections, including influenza a virus and sars coronavirus. to further analyze the microbiological status of ferrets, their fecal viral flora was studied using a metagenomics approach. novel viruses from the families picorna-, papilloma-, and anelloviridae as well as known viruses from the families astro-, corona-, parvo-, and hepeviridae were identified in different ferret cohorts. ferret kobu- and hepatitis e virus were ma ...201323977082
evaluation of recombinant 2009 pandemic influenza a (h1n1) viruses harboring zanamivir resistance mutations in mice and ferrets.recombinant influenza a(h1n1)pdm09 wild-type (wt) and zanamivir-resistant e119g and q136k neuraminidase mutants were generated to determine their enzymatic and replicative properties in vitro, as well as their infectivity and transmissibility in mice and ferrets. viral titers of recombinant e119g and q136k mutants were significantly lower than those of the wt in the first 36 h postinoculation (p.i.) in vitro. the e119g and q136k mutations were both associated with a significant reduction of tota ...201323357777
antigenic characterization of h3n2 influenza a viruses from ohio agricultural fairs.the demonstrated link between the emergence of h3n2 variant (h3n2v) influenza a viruses (iavs) and swine exposure at agricultural fairs has raised concerns about the human health risk posed by iav-infected swine. understanding the antigenic profiles of iavs circulating in pigs at agricultural fairs is critical to developing effective prevention and control strategies. here, 68 h3n2 iav isolates recovered from pigs at ohio fairs (2009 to 2011) were antigenically characterized. these isolates were ...201323637412
economic analysis of pandemic influenza mitigation strategies for five pandemic severity categories.the threat of emergence of a human-to-human transmissible strain of highly pathogenic influenza a(h5n1) is very real, and is reinforced by recent results showing that genetically modified a(h5n1) may be readily transmitted between ferrets. public health authorities are hesitant in introducing social distancing interventions due to societal disruption and productivity losses. this study estimates the effectiveness and total cost (from a societal perspective, with a lifespan time horizon) of a com ...201323496898
considerations regarding appropriate sample size for conducting ferret transmission experiments.evaluation of: nishiura h, yen h-l, cowling bj. sample size considerations for one-to-one animal transmission studies of the influenza a viruses. plos one 8(1), e55358 (2013). there is an urgent need to model in a laboratory setting the capacity of wild-type influenza viruses to transmit between mammals, to determine the molecular determinants and identify biological properties that confer influenza virus transmissibility, and to explore both pharmaceutical and nonpharmaceutical methods to inhib ...201323902143
an in vivo human-plasmablast enrichment technique allows rapid identification of therapeutic influenza a antibodies.recent advances enabling the cloning of human immunoglobulin g genes have proven effective for discovering monoclonal antibodies with therapeutic potential. however, these antibody-discovery methods are often arduous and identify only a few candidates from numerous antibody-secreting plasma cells or plasmablasts. we describe an in vivo enrichment technique that identifies broadly neutralizing human antibodies with high frequency. for this technique, human peripheral blood mononuclear cells from ...201323870317
clinical profiles associated with influenza disease in the ferret model.influenza a viruses continue to pose a threat to human health; thus, various vaccines and prophylaxis continue to be developed. testing of these products requires various animal models including mice, guinea pigs, and ferrets. however, because ferrets are naturally susceptible to infection with human influenza viruses and because the disease state resembles that of human influenza, these animals have been widely used as a model to study influenza virus pathogenesis. in this report, a statistical ...201323472182
development of a neutralization assay for influenza virus using an endpoint assessment based on quantitative reverse-transcription pcr.a microneutralization assay using an elisa-based endpoint assessment (elisa-mn) is widely used to measure the serological response to influenza virus infection and vaccination. we have developed an alternative microneutralization assay for influenza virus using a quantitative reverse transcription pcr-based endpoint assessment (qpcr-mn) in order to improve upon technical limitations associated with elisa-mn. for qpcr-mn, infected mdck-london cells in 96-well cell-culture plates are processed wit ...201323437084
sample size considerations for one-to-one animal transmission studies of the influenza a viruses.animal transmission studies can provide important insights into host, viral and environmental factors affecting transmission of viruses including influenza a. the basic unit of analysis in typical animal transmission experiments is the presence or absence of transmission from an infectious animal to a susceptible animal. in studies comparing two groups (e.g. two host genetic variants, two virus strains, or two arrangements of animal cages), differences between groups are evaluated by comparing t ...201323383167
type i ifn triggers rig-i/tlr3/nlrp3-dependent inflammasome activation in influenza a virus infected cells.influenza a virus (iav) triggers a contagious and potentially lethal respiratory disease. a protective il-1β response is mediated by innate receptors in macrophages and lung epithelial cells. nlrp3 is crucial in macrophages; however, which sensors elicit il-1β secretion in lung epithelial cells remains undetermined. here, we describe for the first time the relative roles of the host innate receptors rig-i (ddx58), tlr3, and nlrp3 in the il-1β response to iav in primary lung epithelial cells. to ...201323592984
novel avian-origin influenza a (h7n9) virus attachment to the respiratory tract of five animal models.we determined the pattern of attachment of the avian-origin h7n9 influenza viruses a/anhui/1/2013 and a/shanghai/1/2013 to the respiratory tract in ferrets, macaques, mice, pigs, and guinea pigs and compared it to that in humans. the h7n9 attachment pattern in macaques, mice, and to a lesser extent pigs and guinea pigs resembled that in humans more closely than the attachment pattern in ferrets. this information contributes to our knowledge of the different animal models for influenza.201424478425
next-generation sequencing and bioinformatic approaches to detect and analyze influenza virus in ferrets.conventional methods used to detect and characterize influenza viruses in biological samples face multiple challenges due to the diversity of subtypes and high dissimilarity of emerging strains. next-generation sequencing (ngs) is a powerful technique that can facilitate the detection and characterization of influenza, however, the sequencing strategy and the procedures of data analysis possess different aspects that require careful consideration.201424727517
zanamivir conjugated to poly-l-glutamine is much more active against influenza viruses in mice and ferrets than the drug itself.previously, polymer-attached zanamivir had been found to inhibit influenza a viruses in vitro far better than did small-molecule zanamivir (1) itself. the aim of this study was to identify in vitro-using the plaque reduction assay-a highly potent 1-polymer conjugate, and subsequently test its antiviral efficacy in vivo.201424065587
adjuvanted inactivated influenza a(h3n2) vaccines induce stronger immunogenicity in mice and confer higher protection in ferrets than unadjuvanted inactivated vaccines.influenza viruses are major respiratory pathogens and the development of improved vaccines to prevent these infections is of high priority. here, we evaluated split inactivated a(h3n2) vaccines (a/uruguay/716/2007) combined or not with adjuvants (as03, as25 and protollin) and administered by three different routes, intramuscular (i.m.), intranasal (i.n.) or intradermal (i.d.), both in balb/c mice and in ferrets. ferrets were challenged with the homologous strain a/uruguay/716/2007 (h3n2) or the ...201425173481
impaired heterologous immunity in aged ferrets during sequential influenza a h1n1 infection.the major burden of influenza morbidity resides within the elderly population. the challenge managing influenza-associated illness in the elderly is the decline of immune function, where mechanisms leading to immunological senescence have not been elucidated. to better represent the immune environment, we investigated clinical morbidity and immune function during sequential homologous and heterologous h1n1 influenza infection in an aged ferret model. our findings demonstrated experimentally that ...201425086242
avian influenza h7n9/13 and h7n7/13: a comparative virulence study in chickens, pigeons, and ferrets.human influenza cases caused by a novel avian h7n9 virus in china emphasize the zoonotic potential of that subtype. we compared the infectivity and pathogenicity of the novel h7n9 virus with those of a recent european avian h7n7 strain in chickens, pigeons, and ferrets. neither virus induced signs of disease despite substantial replication in inoculated chickens and rapid transmission to contact chickens. evidence of the replication of both viruses in pigeons, albeit at lower levels of rna excre ...201424899194
development of a high-yield live attenuated h7n9 influenza virus vaccine that provides protection against homologous and heterologous h7 wild-type viruses in ferrets.live attenuated h7n9 influenza vaccine viruses that possess the hemagglutinin (ha) and neuraminidase (na) gene segments from the newly emerged wild-type (wt) a/anhui/1/2013 (h7n9) and six internal protein gene segments from the cold-adapted influenza virus a/ann arbor/6/60 (aa ca) were generated by reverse genetics. the reassortant virus containing the original wt a/anhui/1/2013 ha and na sequences replicated poorly in eggs. multiple variants with amino acid substitutions in the ha head domain t ...201424719414
transmission of h7n9 influenza virus in mice by different infective routes.on 19 february 2013, the first patient infected with a novel influenza a h7n9 virus from an avian source showed symptoms of sickness. more than 349 laboratory-confirmed cases and 109 deaths have been reported in mainland china since then. laboratory-confirmed, human-to-human h7n9 virus transmission has not been documented between individuals having close contact; however, this transmission route could not be excluded for three families. to control the spread of the avian influenza h7n9 virus, we ...201425367670
the r292k mutation that confers resistance to neuraminidase inhibitors leads to competitive fitness loss of a/shanghai/1/2013 (h7n9) influenza virus in ferrets.neuraminidase (na) inhibitors are the only licensed therapeutic option for human zoonotic h7n9 infections. an na-r292k mutation that confers broad-spectrum resistance to na inhibitors has been documented in h7n9 patients after treatment.201424951824
response of mice and ferrets to a monovalent influenza a (h7n9) split vaccine.in early spring 2013, the emergence of the influenza a (h7n9) virus in humans in eastern china raised concerns of a new influenza pandemic. development of a safe and effective h7n9 influenza vaccine is urgently needed. to this end, we first synthesized the hemagglutinin (ha) and neuraminidase (na) genes of the influenza a (h7n9) virus a/anhui/1/2013. using reverse genetics, we rescued a reassortant virus (h7n9/pr8) that contained the ha and na genes from wild-type h7n9 and six genes encoding int ...201424937303
transmissibility of novel h7n9 and h9n2 avian influenza viruses between chickens and ferrets.previous studies have shown that the h7n9 avian influenza virus cannot be transmitted efficiently between ferrets via respiratory droplets. here, we studied the infectivity of the h7n9 avian influenza virus in chickens and its transmissibility from infected to naïve chickens and ferrets. the h7n9 virus (a/anhui/1/2013) replicated poorly in chickens and could not be transmitted efficiently from infected chickens to naïve chickens and ferrets. h7n9 virus was shed from chicken tracheae for only 2 d ...201424503095
an avian h7n1 gain-of-function experiment of great concern.inappropriately named gain-of-function influenza research seeks to confer airborne transmission on avian influenza a viruses that otherwise cause only dead-end infections in humans. a recent study has succeeded in doing this with a highly pathogenic ostrich h7n1 virus in a ferret model without loss of virulence. if transposable to humans, this would constitute a novel virus with a case fatality rate ~30 greater than that of spanish flu. a commentary from three distinguished virologists considere ...201425316697
airborne transmission of highly pathogenic h7n1 influenza virus in ferrets.avian h7 influenza viruses are recognized as potential pandemic viruses, as personnel often become infected during poultry outbreaks. h7 infections in humans typically cause mild conjunctivitis; however, the h7n9 outbreak in the spring of 2013 has resulted in severe respiratory disease. to date, no h7 viruses have acquired the ability for sustained transmission among humans. airborne transmission is considered a requirement for the emergence of pandemic influenza, and advanced knowledge of the m ...201424696487
animal models for influenza virus pathogenesis, transmission, and immunology.in humans, infection with an influenza a or b virus manifests typically as an acute and self-limited upper respiratory tract illness characterized by fever, cough, sore throat, and malaise. however, influenza can present along a broad spectrum of disease, ranging from sub-clinical or even asymptomatic infection to a severe primary viral pneumonia requiring advanced medical supportive care. disease severity depends upon the virulence of the influenza virus strain and the immune competence and pre ...201424709389
genetics, receptor binding property, and transmissibility in mammals of naturally isolated h9n2 avian influenza viruses.h9n2 subtype influenza viruses have been detected in different species of wild birds and domestic poultry in many countries for several decades. because these viruses are of low pathogenicity in poultry, their eradication is not a priority for animal disease control in many countries, which has allowed them to continue to evolve and spread. here, we characterized the genetic variation, receptor-binding specificity, replication capability, and transmission in mammals of a series of h9n2 influenza ...201425411973
ferrets exclusively synthesize neu5ac and express naturally humanized influenza a virus receptors.mammals express the sialic acids n-acetylneuraminic acid (neu5ac) and n-glycolylneuraminic acid (neu5gc) on cell surfaces, where they act as receptors for pathogens, including influenza a virus (iav). neu5gc is synthesized from neu5ac by the enzyme cytidine monophosphate-n-acetylneuraminic acid hydroxylase (cmah). in humans, this enzyme is inactive and only neu5ac is produced. ferrets are susceptible to human-adapted iav strains and have been the dominant animal model for iav studies. here we sh ...201425517696
enhancement of influenza virus transmission by gene reassortment.influenza a virus is characterized by a genome composed of eight single-stranded, negative sense rna segments, which allow for reassortment between different strains when they co-infect the same host cell. reassortment is an important driving force for the evolution of influenza viruses. the ability of reassortment allows influenza virus to endlessly reinvent itself and pose a constant threat to the health of humans and other animals. of the four human influenza pandemics since the beginning of ...201425048543
pandemic potential of avian influenza a (h7n9) viruses.avian influenza viruses rarely infect humans, but the recently emerged avian h7n9 influenza viruses have caused sporadic infections in humans in china, resulting in 440 confirmed cases with 122 fatalities as of 16 may 2014. in addition, epidemiologic surveys suggest that there have been asymptomatic or mild human infections with h7n9 viruses. these viruses replicate efficiently in mammals, show limited transmissibility in ferrets and guinea pigs, and possess mammalian-adapting amino acid changes ...201425264312
glycomic characterization of respiratory tract tissues of ferrets: implications for its use in influenza virus infection studies.the initial recognition between influenza virus and the host cell is mediated by interactions between the viral surface protein hemagglutinin and sialic acid-terminated glycoconjugates on the host cell surface. the sialic acid residues can be linked to the adjacent monosaccharide by α2-3- or α2-6-type glycosidic bonds. it is this linkage difference that primarily defines the species barrier of the influenza virus infection with α2-3 binding being associated with avian influenza viruses and α2-6 ...201425135641
circulating avian influenza viruses closely related to the 1918 virus have pandemic potential.wild birds harbor a large gene pool of influenza a viruses that have the potential to cause influenza pandemics. foreseeing and understanding this potential is important for effective surveillance. our phylogenetic and geographic analyses revealed the global prevalence of avian influenza virus genes whose proteins differ only a few amino acids from the 1918 pandemic influenza virus, suggesting that 1918-like pandemic viruses may emerge in the future. to assess this risk, we generated and charact ...201424922572
pathogenic influenza b virus in the ferret model establishes lower respiratory tract infection.influenza b viruses have become increasingly more prominent during influenza seasons. influenza b infection is typically considered a mild disease and receives less attention than influenza a, but has been causing 20 to 50 % of the total influenza incidence in several regions around the world. although there is increasing evidence of mid to lower respiratory tract diseases such as bronchitis and pneumonia in influenza b patients, little is known about the pathogenesis of recent influenza b virus ...201424989173
detection of evolutionarily distinct avian influenza a viruses in antarctica.abstract distinct lineages of avian influenza viruses (aivs) are harbored by spatially segregated birds, yet significant surveillance gaps exist around the globe. virtually nothing is known from the antarctic. using virus culture, molecular analysis, full genome sequencing, and serology of samples from adélie penguins in antarctica, we confirmed infection by h11n2 subtype aivs. their genetic segments were distinct from all known contemporary influenza viruses, including south american aivs, sugg ...201424803521
natural a(h1n1)pdm09 influenza virus infection case in a pet ferret in taiwan.ferrets have demonstrated high susceptibility to the influenza virus. this study discusses a natural 2009 pandemic influenza a (h1n1) (a(h1n1)pdm09) virus infection in a pet ferret (mustela putorius furo) identified in taiwan in 2013. the ferret was in close contact with family members who had recently experienced an influenza-like illness (ili). the ferret nasal swab showed positive results for influenza a virus using one-step rt-pcr. the virus was isolated and the phylogenetic analysis indicat ...201425597188
severity of clinical disease and pathology in ferrets experimentally infected with influenza viruses is influenced by inoculum volume.ferrets are a valuable model for influenza virus pathogenesis, virus transmission, and antiviral therapy studies. however, the contributions of the volume of inoculum administered and the ferret's respiratory tract anatomy to disease outcome have not been explored. we noted variations in clinical disease outcomes and the volume of inoculum administered and investigated these differences by administering two influenza viruses (a/california/07/2009 [h1n1 pandemic] and a/minnesota/11/2010 [h3n2 var ...201425187553
heterogeneous pathological outcomes after experimental ph1n1 influenza infection in ferrets correlate with viral replication and host immune responses in the lung.the swine-origin pandemic (p) h1n1 influenza a virus causes mild upper-respiratory tract disease in most human patients. however, some patients developed severe lower-respiratory tract infections with fatal consequences, and the cause of these infections remain unknown. recently, it has been suggested that different populations have different degrees of susceptibility to ph1n1 strains due to host genetic variations that are associated with inappropriate immune responses against viral genetic cha ...201425163545
the temperature-sensitive and attenuation phenotypes conferred by mutations in the influenza virus pb2, pb1, and np genes are influenced by the species of origin of the pb2 gene in reassortant viruses derived from influenza a/california/07/2009 and a/wsn/33 viruses.live attenuated influenza vaccines in the united states are derived from a human virus that is temperature sensitive (ts), characterized by restricted (≥ 100-fold) replication at 39 °c. the ts genetic signature (ts sig) has been mapped to 5 loci in 3 genes: pb1 (391 e, 581 g, and 661 t), pb2 (265 s), and np (34 g). however, when transferred into avian and swine influenza viruses, only partial ts and attenuation phenotypes occur. to investigate the reason for this, we introduced the ts sig into t ...201425122786
influenza a virus acquires enhanced pathogenicity and transmissibility after serial passages in swine.genetic and phylogenetic analyses suggest that the pandemic h1n1/2009 virus was derived from well-established swine influenza lineages; however, there is no convincing evidence that the pandemic virus was generated from a direct precursor in pigs. furthermore, the evolutionary dynamics of influenza virus in pigs have not been well documented. here, we subjected a recombinant virus (rh1n1) with the same constellation makeup as the pandemic h1n1/2009 virus to nine serial passages in pigs. the seve ...201425100840
effect of receptor binding specificity on the immunogenicity and protective efficacy of influenza virus a h1 vaccines.the biological basis for the poor immunogenicity of unadjuvanted avian influenza a virus vaccines in mammals is not well understood. here, we mutated the hemagglutinin (ha) of two h1n1 virus vaccines to determine whether virus receptor binding specificity contributes to the low immunogenicity of avian influenza virus vaccines. mutations were introduced into the ha of an avian influenza virus, a/duck/new york/15024-21/96 (dk/96) which switched the binding preference from α2,3- to α2,6-linked sial ...201425078114
evaluation of oseltamivir prophylaxis regimens for reducing influenza virus infection, transmission and disease severity in a ferret model of household contact.the emergence of the pandemic influenza a(h1n1)pdm09 virus in 2009 saw a significant increase in the therapeutic and prophylactic use of neuraminidase inhibitors (nais) to mitigate the impact of this highly transmissible virus. prior to the pandemic, many countries stockpiled nais and developed pandemic plans for the use of antiviral drugs, based on either treatment of high-risk individuals and/or prophylaxis of contacts. however, to date there has been a lack of in vivo models to test the effic ...201424840623
estimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant a(h1n1)pdm09 influenza viruses.oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection. surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses. since the emergence of the pandemic 2009 a(h1n1) influenza virus (a(h1n1)pdm09), the proportion of a(h1n1)pdm09 viruses that are oseltamivir resistant (or) has generally been low. however, a cluster of or a(h1n1)pdm09 viruses, encoding the neuraminidase ( ...201424699865
the pathology and pathogenesis of experimental severe acute respiratory syndrome and influenza in animal models.respiratory viruses that emerge in the human population may cause high morbidity and mortality, as well as concern about pandemic spread. examples are severe acute respiratory syndrome coronavirus (sars-cov) and novel variants of influenza a virus, such as h5n1 and pandemic h1n1. different animal models are used to develop therapeutic and preventive measures against such viruses, but it is not clear which are most suitable. therefore, this review compares animal models of sars and influenza, wit ...201424581932
influenza a virus infections in marine mammals and terrestrial carnivores.influenza a viruses (iav), members of the orthomyxoviridae, cover a wide host spectrum comprising a plethora of avian and, in comparison, a few mammalian species. the viral reservoir and gene pool are kept in metapopulations of aquatic wild birds. the mammalian-adapted iavs originally arose by transspecies transmission from avian sources. in swine, horse and man, species-adapted iav lineages circulate independently of the avian reservoir and cause predominantly respiratory disease of highly vari ...201424511825
evaluation of heterosubtypic cross-protection against highly pathogenic h5n1 by active infection with human seasonal influenza a virus or trivalent inactivated vaccine immunization in ferret models.the threat of highly pathogenic avian influenza (hpai) h5n1 viruses to cause the next pandemic remains a major concern. here, we evaluated the cross-protection induced by natural infection of human seasonal influenza strains or immunization with trivalent inactivated influenza vaccine (tiv) against hpai h5n1 (a/vietnam/1203/2004) virus in ferrets. groups were treated with pbs (group a), infected with h1n1 (group b) or h3n2 (group c) virus, or immunized with tiv (group d). twelve weeks after the ...201424421115
impact of potential permissive neuraminidase mutations on viral fitness of the h275y oseltamivir-resistant influenza a(h1n1)pdm09 virus in vitro, in mice and in ferrets.neuraminidase (na) mutations conferring resistance to na inhibitors (nais) generally compromise the fitness of influenza viruses. the only nai-resistant virus that widely spread in the population, the a/brisbane/59/2007 (h1n1) strain, contained permissive mutations that restored the detrimental effect caused by the h275y change. computational analysis predicted other permissive na mutations for a(h1n1)pdm09 viruses. here, we investigated the effect of t289m and n369k mutations on the viral fitne ...201424257597
alternative reassortment events leading to transmissible h9n1 influenza viruses in the ferret model.influenza a h9n2 viruses are common poultry pathogens that occasionally infect swine and humans. it has been shown previously with h9n2 viruses that reassortment can generate novel viruses with increased transmissibility. here, we demonstrate the modeling power of a novel transfection-based inoculation system to select reassortant viruses under in vivo selective pressure. plasmids containing the genes from an h9n2 virus and a pandemic h1n1 (ph1n1) virus were transfected into hek 293t cells to po ...201424131710
novel avian-origin human influenza a(h7n9) can be transmitted between ferrets via respiratory droplets.the outbreak of human infections caused by novel avian-origin influenza a(h7n9) in china since march 2013 underscores the need to better understand the pathogenicity and transmissibility of these viruses in mammals. in a ferret model, the pathogenicity of influenza a(h7n9) was found to be less than that of an influenza a(h5n1) strain but comparable to that of 2009 pandemic influenza a(h1n1), based on the clinical signs, mortality, virus dissemination, and results of histopathologic analyses. inf ...201423990570
respiratory transmission of an avian h3n8 influenza virus isolated from a harbour seal.the ongoing human h7n9 influenza infections highlight the threat of emerging avian influenza viruses. in 2011, an avian h3n8 influenza virus isolated from moribund new england harbour seals was shown to have naturally acquired mutations known to increase the transmissibility of highly pathogenic h5n1 influenza viruses. to elucidate the potential human health threat, here we evaluate a panel of avian h3n8 viruses and find that the harbour seal virus displays increased affinity for mammalian recep ...201425183346
development of a surveillance scheme for equine influenza in the uk and characterisation of viruses isolated in europe, dubai and the usa from 2010-2012.equine influenza viruses are a major cause of respiratory disease in horses worldwide and undergo antigenic drift. several outbreaks of equine influenza occurred worldwide during 2010-2012, including in vaccinated animals, highlighting the importance of surveillance and virus characterisation. virus isolates were characterised from more than 20 outbreaks over a 3-year period, including strains from the uk, dubai, germany and the usa. the haemagglutinin-1 (ha1) sequence of all isolates was determ ...201424480583
development and pre-clinical evaluation of two laiv strains against potentially pandemic h2n2 influenza virus.h2n2 influenza a caused the asian flu pandemic in 1957, circulated for more than 10 years and disappeared from the human population after 1968. given that people born after 1968 are naïve to h2n2, that the virus still circulates in wild birds and that this influenza subtype has a proven pandemic track record, h2n2 is regarded as a potential pandemic threat. to prepare for an h2n2 pandemic, here we developed and tested in mice and ferrets two live attenuated influenza vaccines based on the haemag ...201425058039
risk assessment of h2n2 influenza viruses from the avian reservoir.h2n2 influenza a viruses were the cause of the 1957-1958 pandemic. historical evidence demonstrates they arose from avian virus ancestors, and while the h2n2 subtype has disappeared from humans, it persists in wild and domestic birds. reemergence of h2n2 in humans is a significant threat due to the absence of humoral immunity in individuals under the age of 50. thus, examination of these viruses, particularly those from the avian reservoir, must be addressed through surveillance, characterizatio ...201424227848
live attenuated influenza h7n3 vaccine is safe, immunogenic and confers protection in animal models.in 2003 the outbreak of highly pathogenic h7 avian influenza occurred in the netherlands. the avian h7 virus causing the outbreak was also detected in humans; one person died of pneumonia and acute respiratory distress syndrome. our paper describes preclinical studies of a h7n3 live attenuated influenza a vaccine (laiv) candidate in various animal models.201425685247
performance characteristics of qualified cell lines for isolation and propagation of influenza viruses for vaccine manufacturing.cell culture is now available as a method for the production of influenza vaccines in addition to eggs. in accordance with currently accepted practice, viruses recommended as candidates for vaccine manufacture are isolated and propagated exclusively in hens' eggs prior to distribution to manufacturers. candidate vaccine viruses isolated in cell culture are not available to support vaccine manufacturing in mammalian cell bioreactors so egg-derived viruses have to be used. recently influenza a (h3 ...201424975811
pathobiological features of a novel, highly pathogenic avian influenza a(h5n8) virus.the endemicity of highly pathogenic avian influenza (hpai) a(h5n1) viruses in asia has led to the generation of reassortant h5 strains with novel gene constellations. a newly emerged hpai a(h5n8) virus caused poultry outbreaks in the republic of korea in 2014. because newly emerging high-pathogenicity h5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. here, we characterized a/mallard duck/korea/w452/2014 (mdk/w452(h5n8)), a repres ...201426038499
identification of molecular markers associated with alteration of receptor-binding specificity in a novel genotype of highly pathogenic avian influenza a(h5n1) viruses detected in cambodia in 2013.human infections with influenza a(h5n1) virus in cambodia increased sharply during 2013. molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with the alteration of receptor-binding specificity (k189r, q222l) and respiratory droplet transmission in ferrets (n220k with q222l). discovery of quasispecies at position 222 (q/l), in addition to the absence of the mutations in poultry/environmental samples, suggested that th ...201425210193
mammalian models for the study of h7 virus pathogenesis and transmission.mammalian models, most notably the mouse and ferret, have been instrumental in the assessment of avian influenza virus pathogenicity and transmissibility, and have been used widely to characterize the molecular determinants that confer h5n1 virulence in mammals. however, while h7 influenza viruses have typically been associated with conjunctivitis and/or mild respiratory disease in humans, severe disease and death is also possible, as underscored by the recent emergence of h7n9 viruses in china. ...201424996862
high doses of highly pathogenic avian influenza virus in chicken meat are required to infect ferrets.high pathogenicity avian influenza viruses (hpaiv) have caused fatal infections in mammals through consumption of infected bird carcasses or meat, but scarce information exists on the dose of virus required and the diversity of hpaiv subtypes involved. ferrets were exposed to different hpaiv (h5 and h7 subtypes) through consumption of infected chicken meat. the dose of virus needed to infect ferrets through consumption was much higher than via respiratory exposure and varied with the virus strai ...201424894438
african green monkeys recapitulate the clinical experience with replication of live attenuated pandemic influenza virus vaccine candidates.live attenuated cold-adapted (ca) h5n1, h7n3, h6n1, and h9n2 influenza vaccine viruses replicated in the respiratory tract of mice and ferrets, and 2 doses of vaccines were immunogenic and protected these animals from challenge infection with homologous and heterologous wild-type (wt) viruses of the corresponding subtypes. however, when these vaccine candidates were evaluated in phase i clinical trials, there were inconsistencies between the observations in animal models and in humans. the vacci ...201424807726
identification, characterization, and natural selection of mutations driving airborne transmission of a/h5n1 virus.recently, a/h5n1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. the critical genetic changes in airborne a/indonesia/5/05 were not yet identified. here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. substitutions in pb1 and pb2 collectively caused enhanced transcription and virus replication. one substitution increased ha thermostability and lowered the ph of membrane f ...201424725402
highly pathogenic avian influenza a virus (h5n1) can be transmitted in ferrets by transfusion.highly pathogenic avian influenza a virus has been shown to infect organs other than the lung, and this is likely to be mediated by systemic spread resulting from viremia which has been detected in blood in severe cases of infection with avian h5n1 viruses. the infectivity of virus in blood and the potential for virus transmission by transfusion has not been investigated.201424712669
a novel neutralizing antibody against diverse clades of h5n1 influenza virus and its mutants capable of airborne transmission.highly pathogenic avian influenza a virus h5n1 continues to spread among poultry and has frequently broken the species barrier to humans. recent studies have shown that a laboratory-mutated or reassortant h5n1 virus bearing hemagglutinin (ha) with as few as four or five mutations was capable of transmitting more efficiently via respiratory droplets between ferrets, posing a serious threat to public health and underscoring the priority of effective vaccines and therapeutics. in this study, we ide ...201424681124
a model for early onset of protection against lethal challenge with highly pathogenic h5n1 influenza virus.highly pathogenic avian influenza viruses of subtype h5n1 sporadically cause severe disease in humans and involve the risk of inducing a pandemic by gaining the ability for human-to-human transmission. in naïve poultry, primarily gallinaceous birds, the virus induces fatal disease and the used inactivated vaccines occasionally are unable to provide efficient and early onset of protection. therefore, optimized vaccines must be developed and evaluated in model systems. in our study, we tested a no ...201424674664
intranasal vaccination with a plant-derived h5 ha vaccine protects mice and ferrets against highly pathogenic avian influenza virus challenge.highly pathogenic avian influenza h5n1 infection remains a public health threat and vaccination is the best measure of limiting the impact of a potential pandemic. mucosal vaccines have the advantage of eliciting immune responses at the site of viral entry, thereby preventing infection as well as further viral transmission. in this study, we assessed the protective efficacy of hemagglutinin (ha) from the a/indonesia/05/05 (h5n1) strain of influenza virus that was produced by transient expression ...201525714901
pb2 segment promotes high-pathogenicity of h5n1 avian influenza viruses in mice.h5n1 influenza viruses with high lethality are a continuing threat to humans and poultry. recently, h5n1 high-pathogenicity avian influenza virus (hpaiv) has been shown to transmit through aerosols between ferrets in lab experiments by acquiring some mutation. this is another deeply aggravated threat of h5n1 hpaiv to humans. to further explore the molecular determinant of h5n1 hpaiv virulence in a mammalian model, we compared the virulence of a/duck/guangdong/212/2004 (dk212) and a/quail/guangdo ...201525713566
an anti-h5n1 influenza virus fcdart antibody is a highly efficacious therapeutic agent and prophylactic against h5n1 influenza virus infection.highly pathogenic h5n1 avian influenza viruses are associated with severe disease in humans and continue to be a pandemic threat. while vaccines are available, other approaches are required for patients that typically respond poorly to vaccination, such as the elderly and the immunocompromised. to produce a therapeutic agent that is highly efficacious at low doses and is broadly specific against antigenically drifted h5n1 influenza viruses, we developed two neutralizing monoclonal antibodies and ...201525673719
intranasal immunization of recombinant lactococcus lactis induces protection against h5n1 virus in ferrets.the increasing outbreaks of highly pathogenic avian influenza a (hpai) h5n1 viruses in birds and human bring out an urgent need to develop a safe and effective vaccine to control and prevent h5n1 infection. lactococcus lactis (l. lactis) based vaccine platform is a promising approach for mucosal h5n1 vaccine development. intranasal immunization is the potential to induce mucosal immune response which is associated with protective immunity. to develop a safe and effective mucosal vaccine against ...201525445345
low virulence and lack of airborne transmission of the dutch highly pathogenic avian influenza virus h5n8 in ferrets.highly pathogenic avian influenza (hpai) h5n8 viruses that emerged in poultry in east asia spread to europe and north america by late 2014. here we show that the european hpai h5n8 viruses differ from the korean and japanese hpai h5n8 viruses by several amino acids and that a dutch hpai h5n8 virus had low virulence and was not transmitted via the airborne route in ferrets. the virus did not cross-react with sera raised against pre-pandemic h5 vaccine strains. this data is useful for public healt ...201526090682
pathogenesis of novel reassortant avian influenza virus a (h5n8) isolates in the ferret.outbreaks of avian influenza virus h5n8 first occurred in 2014, and spread to poultry farms in korea. although there was no report of human infection by this subtype, it has the potential to threaten human public health. therefore, we evaluated the pathogenesis of h5n8 viruses in ferrets. two representative korean h5n8 strains did not induce mortality and significant respiratory signs after an intranasal challenge in ferrets. however, ferrets intratracheally infected with a/broiler duck/korea/bu ...201525776760
replication of live attenuated cold-adapted h2n2 influenza virus vaccine candidates in non human primates.the development of an h2n2 vaccine is a priority in pandemic preparedness planning. we previously showed that a single dose of a cold-adapted (ca) h2n2 live attenuated influenza vaccine (laiv) based on the influenza a/ann arbor/6/60 (aa ca) virus was immunogenic and efficacious in mice and ferrets. however, in a phase i clinical trial, viral replication was restricted and immunogenicity was poor. in this study, we compared the replication of four h2n2 laiv candidate viruses, aa ca, a/tecumseh/3/ ...201525444799
a live attenuated equine h3n8 influenza vaccine is highly immunogenic and efficacious in mice and ferrets.equine influenza viruses (eiv) are responsible for rapidly spreading outbreaks of respiratory disease in horses. although natural infections of humans with eiv have not been reported, experimental inoculation of humans with these viruses can lead to a productive infection and elicit a neutralizing antibody response. moreover, eiv have crossed the species barrier to infect dogs, pigs, and camels and therefore may also pose a threat to humans. based on serologic cross-reactivity of h3n8 eiv from d ...201525410860
generation and characterization of live attenuated influenza a(h7n9) candidate vaccine virus based on russian donor of attenuation.avian influenza a (h7n9) virus has emerged recently and continues to cause severe disease with a high mortality rate in humans prompting the development of candidate vaccine viruses. live attenuated influenza vaccines (laiv) are 6:2 reassortant viruses containing the ha and na gene segments from wild type influenza viruses to induce protective immune responses and the six internal genes from master donor viruses (mdv) to provide temperature sensitive, cold-adapted and attenuated phenotypes.201526405798
a single dose of an avian h3n8 influenza virus vaccine is highly immunogenic and efficacious against a recently emerged seal influenza virus in mice and ferrets.h3n8 influenza viruses are a commonly found subtype in wild birds, usually causing mild or no disease in infected birds. however, they have crossed the species barrier and have been associated with outbreaks in dogs, pigs, donkeys, and seals and therefore pose a threat to humans. a live attenuated, cold-adapted (ca) h3n8 vaccine virus was generated by reverse genetics using the wild-type (wt) hemagglutinin (ha) and neuraminidase (na) genes from the a/blue-winged teal/texas/sg-00079/2007 (h3n8) ( ...201525903333
new reassortant and enzootic european swine influenza viruses transmit efficiently through direct contact in the ferret model.the reverse zoonotic events that introduced the 2009 pandemic influenza virus into pigs have drastically increased the diversity of swine influenza viruses in europe. the pandemic potential of these novel reassortments is still unclear, necessitating enhanced surveillance of european pigs with additional focus on risk assessment of these new viruses. in this study, four european swine influenza viruses were assessed for their zoonotic potential. two of the four viruses were enzootic viruses of s ...201525701826
oseltamivir population pharmacokinetics in the ferret: model application for pharmacokinetic/pharmacodynamic study design.the ferret is a suitable small animal model for preclinical evaluation of efficacy of antiviral drugs against various influenza strains, including highly pathogenic h5n1 viruses. rigorous pharmacokinetics/pharmacodynamics (pk/pd) assessment of ferret data has not been conducted, perhaps due to insufficient information on oseltamivir pk. here, based on pk data from several studies on both uninfected and influenza-infected groups (i.e., with influenza a viruses of h5n1 and h3n2 subtypes and an inf ...201526460484
[virological characteristics of influenza a (h3n2) virus in mainland china during 2013-2014].to analyze the antigenic and genetic characteristics of the influenza a (h3n2) virus in mainland china during the surveillance year of 2013-2014, the antigenic characteristics of h3n2 virus were analyzed using reference ferret anti-sera. the nucleotide sequences of the viruses were determined by sanger dideoxy sequencing, phylogenetic trees were constructed with the neighbor-joining method, and the genetic characteristics of the viruses were determined in comparison to current vaccine strains. t ...201525997327
environmental conditions affect exhalation of h3n2 seasonal and variant influenza viruses and respiratory droplet transmission in ferrets.the seasonality of influenza virus infections in temperate climates and the role of environmental conditions like temperature and humidity in the transmission of influenza virus through the air are not well understood. using ferrets housed at four different environmental conditions, we evaluated the respiratory droplet transmission of two influenza viruses (a seasonal h3n2 virus and an h3n2 variant virus, the etiologic virus of a swine to human summertime infection) and concurrently characterize ...201525969995
the repeated introduction of the h3n2 virus from human to swine during 1979-1993 in china.limited data are available regarding the swine influenza viruses (sivs) that circulated in mainland china prior to the 1990s. eleven h3n2 virus strains were isolated from swine populations from 1979 to 1992. to determine the origin and tendency of these sivs, the phylogenetic and antigenic properties of these viruses were analyzed based on the whole genome sequenced and the hi titrations with post-infection ferret antisera against influenza a (h3n2) virus isolates of swine and human origin. the ...201525858119
optimization of an enzyme-linked lectin assay suitable for rapid antigenic characterization of the neuraminidase of human influenza a(h3n2) viruses.antibodies to neuraminidase (na), the second most abundant surface protein of the influenza virus, contribute to protection against influenza virus infection. although traditional and miniaturized thiobarbituric acid (tba) neuraminidase inhibition (ni) assays have been successfully used to characterize the antigenic properties of na, these methods are cumbersome and not easily amendable to rapid screening. an additional difficulty of the ni assay is the interference by hemagglutinin (ha)-specifi ...201525712563
comparative analysis of virulence of a novel, avian-origin h3n2 canine influenza virus in various host species.a novel avian-origin h3n2 canine influenza a virus (civ) that showed high sequence similarities in hemagglutinin and neuraminidase genes with those of non-pathogenic avian influenza viruses was isolated in our routine surveillance program in south korea. we previously reported that the pathogenicity of this strain could be reproduced in dogs and cats. in the present study, the host tropism of h3n2 civ was examined by experimental inoculation into several host species, including chickens, pigs, m ...201525218482
h3n2 canine influenza virus with the matrix gene from the pandemic a/h1n1 virus: infection dynamics in dogs and ferrets.after an outbreak of pandemic influenza a/h1n1 (ph1n1) virus, we had previously reported the emergence of a recombinant canine influenza virus (civ) between the ph1n1 virus and the classic h3n2 civ. our ongoing routine surveillance isolated another reassortant h3n2 civ carrying the matrix gene of the ph1n1 virus from 2012. the infection dynamics of this h3n2 civ variant (civ/h3n2mv) were investigated in dogs and ferrets via experimental infection and transmission. the civ/h3n2mv-infected dogs an ...201524977303
pathogenesis of infection with 2009 pandemic h1n1 influenza virus in isogenic guinea pigs after intranasal or intratracheal inoculation.to elucidate the pathogenesis and transmission of influenza virus, the ferret model is typically used. to investigate protective immune responses, the use of inbred mouse strains has proven invaluable. here, we describe a study with isogenic guinea pigs, which would uniquely combine the advantages of the mouse and ferret models for influenza virus infection. strain 2 isogenic guinea pigs were inoculated with h1n1pdm09 influenza virus a/netherlands/602/09 by the intranasal or intratracheal route. ...201525555619
characterization of the localized immune response in the respiratory tract of ferrets following infection with influenza a and b viruses.the burden of infection with seasonal influenza viruses is significant. each year is typically characterized by the dominance of one (sub)type or lineage of influenza a or b virus, respectively. the incidence of disease varies annually, and while this may be attributed to a particular virus strain or subtype, the impacts of prior immunity, population differences, and variations in clinical assessment are also important. to improve our understanding of the impacts of seasonal influenza viruses, w ...201526719259
lower respiratory tract infection of the ferret by 2009 h1n1 pandemic influenza a virus triggers biphasic, systemic, and local recruitment of neutrophils.infection of the lower respiratory tract by influenza a viruses results in increases in inflammation and immune cell infiltration in the lung. the dynamic relationships among the lung microenvironments, the lung, and systemic host responses during infection remain poorly understood. here we used extensive systematic histological analysis coupled with live imaging to gain access to these relationships in ferrets infected with the 2009 h1n1 pandemic influenza a virus (h1n1pdm virus). neutrophil le ...201526063430
evaluation of the zoonotic potential of a novel reassortant h1n2 swine influenza virus with gene constellation derived from multiple viral sources.in 2011-2012, contemporary north american-like h3n2 swine influenza viruses (sivs) possessing the 2009 pandemic h1n1 matrix gene (h3n2pm-like virus) were detected in domestic pigs of south korea where h1n2 siv strains are endemic. more recently, we isolated novel reassortant h1n2 sivs bearing the eurasian avian-like swine h1-like hemagglutinin and korean swine h1n2-like neuraminidase in the internal gene backbone of the h3n2pm-like virus. in the present study, we clearly provide evidence on the ...201526051886
evaluation of a dry powder delivery system for laninamivir in a ferret model of influenza infection.laninamivir is a long-acting antiviral requiring only a single dose for the treatment of influenza infection, making it an attractive alternative to existing neuraminidase inhibitors that require multiple doses over many days. like zanamivir, laninamivir is administered to patients by inhalation of dry powder. to date, studies investigating the effectiveness of laninamivir or zanamivir in a ferret model of influenza infection have administered the drug in a solubilised form. to better mimic the ...201526022199
replication and transmission of mammalian-adapted h9 subtype influenza virus in pigs and quail.influenza a virus is a major pathogen of birds, swine and humans. strains can jump between species in a process often requiring mutations and reassortment, resulting in outbreaks and, potentially, pandemics. h9n2 avian influenza is predominant in poultry across asia and occasionally infects humans and swine. pandemic h1n1 (h1n1pdm) is endemic in humans and swine and has a history of reassortment in pigs. previous studies have shown the compatibility of h9n2 and h1n1pdm for reassortment in ferret ...201525986634
interval between infections and viral hierarchy are determinants of viral interference following influenza virus infection in a ferret model.epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. this viral interference appears to be independent of any antigenic similarities between the viruses. we used the ferret model of human influenza to systematically investigate viral interference.201525943206
vector optimization and needle-free intradermal application of a broadly protective polyvalent influenza a dna vaccine for pigs and humans.the threat posed by the 2009 pandemic h1n1 virus emphasized the need for new influenza a virus vaccines inducing a broad cross-protective immune response for use in both humans and pigs. an effective and broad influenza vaccine for pigs would greatly benefit the pork industry and contribute to public health by diminishing the risk of emerging highly pathogenic reassortants. current inactivated protein vaccines against swine influenza produce only short-lived immunity and have no efficacy against ...201525746201
the use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893-2014.attempts to reproduce the features of human influenza in laboratory animals date from the early 1890s, when richard pfeiffer inoculated apes with bacteria recovered from influenza patients and produced a mild respiratory illness. numerous studies employing nonhuman primates (nhps) were performed during the 1918 pandemic and the following decade. most used bacterial preparations to infect animals, but some sought a filterable agent for the disease. since the viral etiology of influenza was establ ...201525746173
characterization of a large cluster of influenza a(h1n1)pdm09 viruses cross-resistant to oseltamivir and peramivir during the 2013-2014 influenza season in japan.between september 2013 and july 2014, 2,482 influenza 2009 pandemic a(h1n1) [a(h1n1)pdm09] viruses were screened in japan for the h275y substitution in their neuraminidase (na) protein, which confers cross-resistance to oseltamivir and peramivir. we found that a large cluster of the h275y mutant virus was present prior to the main influenza season in sapporo /: hokkaido, with the detection rate for this mutant virus reaching 29% in this area. phylogenetic analysis suggested the clonal expansion ...201525691635
identification of amino acid substitutions supporting antigenic change of influenza a(h1n1)pdm09 viruses.the majority of currently circulating influenza a(h1n1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. however, antigenic variants are expected to emerge as population immunity increases. amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. in this study, we constructed mutants with substitutions in the hemagglutinin of a/netherlands/602/09 in an atte ...201525609810
sequential infection in ferrets with antigenically distinct seasonal h1n1 influenza viruses boosts hemagglutinin stalk-specific antibodies.broadly reactive antibodies targeting the conserved hemagglutinin (ha) stalk region are elicited following sequential infection or vaccination with influenza viruses belonging to divergent subtypes and/or expressing antigenically distinct ha globular head domains. here, we demonstrate, through the use of novel chimeric ha proteins and competitive binding assays, that sequential infection of ferrets with antigenically distinct seasonal h1n1 (sh1n1) influenza virus isolates induced an ha stalk-spe ...201526559834
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