| comparative pathology in ferrets infected with h1n1 influenza a viruses isolated from different hosts. | virus replication and pulmonary disease pathogenesis in ferrets following intranasal infection with a pandemic influenza strain (a/california/4/09; ca09), a human seasonal influenza h1n1 isolate (a/new caledonia/20/99; ncal99), a classical swine influenza h1n1 isolate (a/swine/iowa/15/30; sw30), or an avian h1n1 isolate (a/mallard/mn/a108-2355/08; mal08) were compared. nasal wash virus titers were similar for ncal99 and sw30 with peak virus titers of 10(5.1) tcid(50)/ml and 10(5.5) tcid(50)/ml o ... | 2011 | 21593156 |
| assessment of the efficacy of the neuraminidase inhibitor oseltamivir against 2009 pandemic h1n1 influenza virus in ferrets. | pandemic 2009 influenza a (h1n1) virus (h1n1pdm) is different from contemporary seasonal human viruses in that it can cause infection deep in the lungs of critical care patients. here we establish a mammalian animal model and assessed the efficacy of the neuraminidase (na) inhibitor oseltamivir treatment against h1n1pdm virus infection. oseltamivir (25mg/kg/day twice daily for 5days) was orally administered to groups of ferrets, starting either 2 or 24h after inoculation with 10(6)pfu of a/calif ... | 2011 | 21635924 |
| pathogenesis of influenza a/h5n1 virus infection in ferrets differs between intranasal and intratracheal routes of inoculation. | most patients infected with highly pathogenic avian influenza a/h5n1 virus develop severe pneumonia resulting in acute respiratory distress syndrome, with extrarespiratory disease as an uncommon complication. intranasal inoculation of ferrets with influenza a/h5n1 virus causes lesions in both the respiratory tract and extrarespiratory organs (primarily brain). however, the route of spread to extrarespiratory organs and the relative contribution of extrarespiratory disease to pathogenicity are la ... | 2011 | 21640972 |
| the ferret as a model organism to study influenza a virus infection. | influenza is a human pathogen that continues to pose a public health threat. the use of small mammalian models has become indispensable for understanding the virulence of influenza viruses. among numerous species used in the laboratory setting, only the ferret model is equally well suited for studying both the pathogenicity and transmissibility of human and avian influenza viruses. here, we compare the advantages and limitations of the mouse, ferret and guinea pig models for research with influe ... | 2011 | 21810904 |
| a neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza a hemagglutinins. | the isolation of broadly neutralizing antibodies against influenza a viruses has been a long-sought goal for therapeutic approaches and vaccine design. using a single-cell culture method for screening large numbers of human plasma cells, we isolated a neutralizing monoclonal antibody that recognized the hemagglutinin (ha) glycoprotein of all 16 subtypes and neutralized both group 1 and group 2 influenza a viruses. passive transfer of this antibody conferred protection to mice and ferrets. comple ... | 2011 | 21798894 |
| dose-response time modeling for highly pathogenic avian influenza a (h5n1) virus infection. | aims: to develop time-dependent dose-response models for highly pathogenic avian influenza a (hpai) of the h5n1 subtype virus. methods and results: a total of four candidate time-dependent dose-response models were fitted to four survival data sets for animals (mice or ferrets) exposed to graded doses of hpai h5n1 virus using the maximum likelihood estimation. a beta-poisson dose-response model with the n(50) parameter modified by an exponential-inverse-power time dependency or an exponential ... | 2011 | 21790679 |
| genetic characterization and pathogenicity assessment of highly pathogenic h5n1 avian influenza viruses isolated from migratory wild birds in 2011, south korea. | the continued spread of a highly pathogenic avian influenza (hpai) h5n1 virus among wild birds and poultry has posed a potential threat to human public health. in the present study, we report the isolation of hpai h5n1 viruses (a/md/korea/w401/11 and a/md/korea/w404/11) from fecal samples of migratory birds. genetic and phlyogenetic analyses demonstrated that these viruses are genetically identical possessing gene segments from avian virus origin and showing highest sequence similarities (as hig ... | 2011 | 21782862 |
| transmissibility of pandemic h1n1 and genetically related swine influenza viruses in ferrets. | | 2011 | 21751464 |
| influenza h5 hemagglutinin dna primes the antibody response elicited by the live attenuated influenza a/vietnam/1203/2004 vaccine in ferrets. | priming immunization plays a key role in protecting individuals or populations to influenza viruses that are novel to humans. to identify the most promising vaccine priming strategy, we have evaluated different prime-boost regimens using inactivated, dna and live attenuated vaccines in ferrets. live attenuated influenza a/vietnam/1203/2004 (h5n1) candidate vaccine (laiv, vn04 ca) primed ferrets efficiently while inactivated h5n1 vaccine could not prime the immune response in seronegative ferrets ... | 2011 | 21760928 |
| compatibility of h9n2 avian influenza surface genes and 2009 pandemic h1n1 internal genes for transmission in the ferret model. | in 2009, a novel h1n1 influenza (ph1n1) virus caused the first influenza pandemic in 40 y. the virus was identified as a triple reassortant between avian, swine, and human influenza viruses, highlighting the importance of reassortment in the generation of viruses with pandemic potential. previously, we showed that a reassortant virus composed of wild-type avian h9n2 surface genes in a seasonal human h3n2 backbone could gain efficient respiratory droplet transmission in the ferret model. here we ... | 2011 | 21730147 |
| hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic h1n1 influenza virus in ferrets. | a novel reassortant derived from north american triple-reassortant (trsw) and eurasian swine (easw) influenza viruses acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. to identify molecular determinants that allowed efficient transmission of the pandemic h1n1 virus among humans, we evaluated the direct-contact and respiratory-droplet transmissibility in ferrets of representative swine influenza viruses of different lineages obtained through a 13-y surveil ... | 2011 | 21825167 |
| role of permissive neuraminidase mutations in influenza a/brisbane/59/2007-like (h1n1) viruses. | neuraminidase (na) mutations conferring resistance to na inhibitors were believed to compromise influenza virus fitness. unexpectedly, an oseltamivir-resistant a/brisbane/59/2007 (bris07)-like h1n1 h275y na variant emerged in 2007 and completely replaced the wild-type (wt) strain in 2008-2009. the na of such variant contained additional na changes (r222q, v234m and d344n) that potentially counteracted the detrimental effect of the h275y mutation on viral fitness. here, we rescued a recombinant b ... | 2011 | 22174688 |
| novel reassortment of eurasian avian-like and pandemic/2009 influenza viruses in swine: infectious potential for humans. | pigs are considered to be intermediate hosts and "mixing vessels," facilitating the genesis of pandemic influenza viruses, as demonstrated by the emergence of the 2009 h1n1 pandemic (pdm/09) virus. the prevalence and repeated introduction of the pdm/09 virus into pigs raises the possibility of generating novel swine influenza viruses with the potential to infect humans. to address this, an active influenza surveillance program was conducted with slaughtered pigs in abattoirs in southern china. o ... | 2011 | 21849442 |
| Generation of recombinant pandemic H1N1 influenza virus with the HA cleavable by bromelain and identification of the residues influencing HA bromelain cleavage. | The proteolytic enzyme bromelain has been traditionally used to cleave the hemagglutinin (HA) protein at the C-terminus of the HA2 region to release the HA proteins from influenza virions. The bromelain cleaved HA (BHA) has been routinely used as an antigen to generate antiserum that is essential for influenza vaccine product release. The HA of the 2009 pandemic H1N1 influenza A/California/7/2009 (CA09) virus could not be cleaved efficiently by bromelain. To ensure timely delivery of BHA for ant ... | 2011 | 22172510 |
| Neuropathology of H5N1 virus infection in ferrets. | Highly pathogenic H5N1 virus remains a potential threat to humans. Over 289 fatalities have been reported in WHO confirmed human cases since 2003, and lack of effective vaccines and early treatments contribute to increasing numbers of cases and fatalities. H5N1 encephalitis is a recognized cause of death in Vietnamese cases, and brain pathology is described in other human cases and naturally infected animals. However, neither pathogenesis of H5N1 viral infection in human brain nor post-infection ... | 2011 | 22176758 |
| in vitro evolution of h5n1 avian influenza virus toward human-type receptor specificity. | acquisition of α2-6 sialoside receptor specificity by α2-3 specific highly-pathogenic avian influenza viruses (h5n1) is thought to be a prerequisite for efficient transmission in humans. by in vitro selection for binding α2-6 sialosides, we identified four variant viruses with amino acid substitutions in the hemagglutinin (s227n, d187g, e190g, and q196r) that revealed modestly increased α2-6 and minimally decreased α2-3 binding by glycan array analysis. however, a mutant virus combining q196r wi ... | 2012 | 22056389 |
| transmission of aerosolized seasonal h1n1 influenza a to ferrets. | influenza virus is a major cause of morbidity and mortality worldwide, yet little quantitative understanding of transmission is available to guide evidence-based public health practice. recent studies of influenza non-contact transmission between ferrets and guinea pigs have provided insights into the relative transmission efficiencies of pandemic and seasonal strains, but the infecting dose and subsequent contagion has not been quantified for most strains. in order to measure the aerosol infect ... | 2011 | 21949718 |
| Assessment of the antiviral properties of recombinant porcine SP-D against various influenza A viruses in vitro. | The emergence of influenza viruses resistant to existing classes of antiviral drugs raises concern and there is a need for novel antiviral agents that could be used therapeutically or prophylacticaly. Surfactant protein D (SP-D) belongs to the family of C-type lectins which are important effector molecules of the innate immune system with activity against bacteria and viruses, including influenza viruses. In the present study we evaluated the potential of recombinant porcine SP-D as an antiviral ... | 2011 | 21935489 |
| multiple reassortment between pandemic (h1n1) 2009 and endemic influenza viruses in pigs, united states. | as a result of human-to-pig transmission, pandemic influenza a (h1n1) 2009 virus was detected in pigs soon after it emerged in humans. in the united states, this transmission was quickly followed by multiple reassortment between the pandemic virus and endemic swine viruses. nine reassortant viruses representing 7 genotypes were detected in commercial pig farms in the united states. field observations suggested that the newly described reassortant viruses did not differ substantially from pandemi ... | 2011 | 21892996 |
| Effect of D222G mutation in the hemagglutinin protein on receptor binding, pathogenesis and transmissibility of the 2009 pandemic H1N1 influenza virus. | Influenza viruses isolated during the 2009 H1N1 pandemic generally lack known molecular determinants of virulence associated with previous pandemic and highly pathogenic avian influenza viruses. The frequency of the amino acid substitution D222G in the hemagglutinin (HA) of 2009 H1N1 viruses isolated from severe but not mild human cases represents the first molecular marker associated with enhanced disease. To assess the relative contribution of this substitution in virus pathogenesis, transmiss ... | 2011 | 21966421 |
| the multi-basic cleavage site of the hemagglutinin of the highly pathogenic a/vietnam/1203/2004 (h5n1) avian influenza virus acts as a virulence factor in a host-specific manner in mammals. | highly pathogenic avian influenza (hpai) viruses of the h5 and h7 subtypes typically possess multiple basic amino acids around the cleavage site (mbs) of their hemagglutinin (ha) protein, a recognized virulence motif in poultry. to determine the importance of the h5 ha mbs as a virulence factor in mammals, recombinant wild-type hpai a/vietnam/1203/2004 (h5n1) viruses that possessed (h5n1) or lacked (δh5n1) the h5 ha mbs were generated and evaluated for their virulence in balb/c mice, ferrets, an ... | 2011 | 22205751 |
| Multidrug resistant 2009 A/H1N1 influenza clinical isolate with a neuraminidase I223R mutation retains its virulence and transmissibility in ferrets. | Only two classes of antiviral drugs, neuraminidase inhibitors and adamantanes, are approved for prophylaxis and therapy against influenza virus infections. A major concern is that influenza virus becomes resistant to these antiviral drugs and spreads in the human population. The 2009 pandemic A/H1N1 influenza virus is naturally resistant to adamantanes. Recently a novel neuraminidase I223R mutation was identified in an A/H1N1 virus showing cross-resistance to the neuraminidase inhibitors oseltam ... | 2011 | 21980293 |
| comparative analyses of pandemic h1n1 and seasonal h1n1, h3n2, and influenza b infections depict distinct clinical pictures in ferrets. | influenza a and b infections are a worldwide health concern to both humans and animals. high genetic evolution rates of the influenza virus allow the constant emergence of new strains and cause illness variation. since human influenza infections are often complicated by secondary factors such as age and underlying medical conditions, strain or subtype specific clinical features are difficult to assess. here we infected ferrets with 13 currently circulating influenza strains (including strains of ... | 2011 | 22110664 |
| Emergence of mammalian species-infectious and -pathogenic avian influenza H6N5 virus with no evidence of adaptation. | The migratory waterfowl of the world are considered to be the natural reservoir of influenza A viruses. Of the 16 hemagglutinin subtypes of avian influenza viruses, the H6 subtype is commonly perpetuated in its natural hosts and is of concern due to its potential to be a precursor of highly pathogenic influenza viruses by reassortment. During routine influenza surveillance, we isolated an unconventional H6N5 subtype of avian influenza virus. Experimental infection of mice revealed that this isol ... | 2011 | 21994462 |
| fitness of neuraminidase inhibitor-resistant influenza a viruses. | antiviral drugs are important components for the control of influenza. the key question is whether antiviral use or natural virus evolution will lead to the emergence of drug-resistant virus with comparable or superior fitness to drug-susceptible counterpart. currently, neuraminidase (na) inhibitors (nais) are the first choice for influenza prevention and treatment. in this article we will review complex process of the risk assessment for the fitness of nais-resistant seasonal h1n1 and h3n2, pan ... | 2011 | 22440915 |
| eurasian-origin gene segments contribute to the transmissibility, aerosol release, and morphology of the 2009 pandemic h1n1 influenza virus. | the epidemiological success of pandemic and epidemic influenza a viruses relies on the ability to transmit efficiently from person-to-person via respiratory droplets. respiratory droplet (rd) transmission of influenza viruses requires efficient replication and release of infectious influenza particles into the air. the 2009 pandemic h1n1 (ph1n1) virus originated by reassortment of a north american triple reassortant swine (trs) virus with a eurasian swine virus that contributed the neuraminidase ... | 2011 | 22241979 |
| 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 ... | 2013 | 23592984 |
| influenza virus vaccine for neglected hosts: horses and dogs. | this study provides information regarding vaccine research and the epidemiology of influenza virus in neglected hosts (horses and dogs). equine influenza virus (eiv) causes a highly contagious disease in horses and other equids, and outbreaks have occurred worldwide. eiv has resulted in costly damage to the horse industry and has the ability of cross the host species barrier from horses to dogs. canine influenza is a virus of equine or avian origin and infects companion animals that live in clos ... | 2016 | 27489801 |
| influenza a (h10n7) virus causes respiratory tract disease in harbor seals and ferrets. | avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype h10n7 (seal/h10n7) in harbor seals (phoca vitulina). this epidemic caused high mortality in seals along the north-west coast of europe and represented a potential risk for human health. to characterize the spectrum of lesions and to identify the target cells and viral ... | 2016 | 27448168 |
| h1n1, but not h3n2, influenza a virus infection protects ferrets from h5n1 encephalitis. | seasonal influenza causes substantial morbidity and mortality because of efficient human-to-human spread. rarely, zoonotic strains of influenza virus spread to humans, where they have the potential to mediate new pandemics with high mortality. we studied systemic viral spread after intranasal infection with highly pathogenic avian influenza virus (h5n1 [a/viet nam/1203/2004]) in ferrets with or without prior pandemic h1n1pdm09 (a/mexico/4108/2009) or h3n2 (a/victoria/361/2011) infection. after i ... | 2013 | 24371072 |
| neurovirulence of h5n1 infection in ferrets is mediated by multifocal replication in distinct permissive neuronal cell regions. | highly pathogenic avian influenza a (hpai), subtype h5n1, remains an emergent threat to the human population. while respiratory disease is a hallmark of influenza infection, h5n1 has a high incidence of neurological sequelae in many animal species and sporadically in humans. we elucidate the temporal/spatial infection of h5n1 in the brain of ferrets following a low dose, intranasal infection of two hpai strains of varying neurovirulence and lethality. a/vietnam/1203/2004 (vn1203) induced mortali ... | 2012 | 23056366 |
| 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. | 2014 | 24478425 |
| evaluation of the human adaptation of influenza a/h7n9 virus in pb2 protein using human and swine respiratory tract explant cultures. | novel avian h7n9 virus emerged in china in 2013 resulting in a case fatality rate of around 39% and continues to pose zoonotic and pandemic risk. amino acid substitutions in pb2 protein were shown to influence the pathogenicity and transmissibility of h7n9 following experimental infection of ferrets and mice. in this study, we evaluated the role of amino acid substitution pb2-627k or compensatory changes at pb2-591k and pb2-701n, on the tropism and replication competence of h7n9 viruses for huma ... | 2016 | 27739468 |
| companion animals as a source of viruses for human beings and food production animals. | companion animals comprise a wide variety of species, including dogs, cats, horses, ferrets, guinea pigs, reptiles, birds and ornamental fish, as well as food production animal species, such as domestic pigs, kept as companion animals. despite their prominent place in human society, little is known about the role of companion animals as sources of viruses for people and food production animals. therefore, we reviewed the literature for accounts of infections of companion animals by zoonotic viru ... | 2016 | 27522300 |
| characterisation of the epidemic strain of h3n8 equine influenza virus responsible for outbreaks in south america in 2012. | an extensive outbreak of equine influenza occurred across multiple countries in south america during 2012. the epidemic was first reported in chile then spread to brazil, uruguay and argentina, where both vaccinated and unvaccinated animals were affected. in brazil, infections were widespread within 3months of the first reported cases. affected horses included animals vaccinated with outdated vaccine antigens, but also with the oie-recommended florida clade 1 strain south africa/4/03. | 2016 | 26993620 |
| safe recombinant outer membrane vesicles that display m2e elicit heterologous influenza protection. | recombinant, escherichia coli-derived outer membrane vesicles (romvs), which display heterologous protein subunits, have potential as a vaccine adjuvant platform. one drawback to romvs is their lipopolysaccharide (lps) content, limiting their translatability to the clinic due to potential adverse effects. here, we explore a unique romv construct with structurally remodeled lipids containing only the lipid iva portion of lps, which does not stimulate human tlr4. the romvs are derived from a genet ... | 2017 | 28215994 |
| enhanced neutralizing antibody titers and th1 polarization from a novel escherichia coli derived pandemic influenza vaccine. | influenza pandemics can spread quickly and cost millions of lives; the 2009 h1n1 pandemic highlighted the shortfall in the current vaccine strategy and the need for an improved global response in terms of shortening the time required to manufacture the vaccine and increasing production capacity. here we describe the pre-clinical assessment of a novel 2009 h1n1 pandemic influenza vaccine based on the e. coli-produced ha globular head domain covalently linked to virus-like particles derived from t ... | 2013 | 24204639 |
| 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 ... | 2014 | 24803521 |
| molecular epidemiology of influenza a(h1n1)pdm09 hemagglutinin gene circulating in são paulo state , brazil: 2016 anticipated influenza season. | compared to previous years, seasonal influenza activity commenced early in são paulo state, brazil, southern hemisphere during the 2016 year. in order to investigate the genetic pattern of influenza a(h1n1)pdm09 in the state of sao paulo a total of 479 respiratory samples, collected in january by sentinel surveillance units, were screened by real-time rt-pcr. a total of 6 influenza viruses a(h1n1)pdm09 presenting ct values ≤ 30 were sequenced following phylogenetic analysis. the present study id ... | 2017 | 28380120 |
| selection of multi-drug resistant influenza a and b viruses under zanamivir pressure and their replication fitness in ferrets. | intravenous zanamivir has been used to treat patients with severe influenza. because the majority of cases (including immunocompromised patients) require the drug for an extended period of treatment, there is a higher risk that the virus will develop resistance. therefore, knowing the possible amino acid substitutions that may arise in recently circulating influenza strains under prolonged zanamivir exposure and their impact on antiviral susceptibility is important. | 2017 | 28195559 |
| swine influenza virus (h1n2) characterization and transmission in ferrets, chile. | phylogenetic analysis of the influenza hemagglutinin gene (ha) has suggested that commercial pigs in chile harbor unique human seasonal h1-like influenza viruses, but further information, including characterization of these viruses, was unavailable. we isolated influenza virus (h1n2) from a swine in a backyard production farm in central chile and demonstrated that the ha gene was identical to that in a previous report. its ha and neuraminidase genes were most similar to human h1 and n2 viruses f ... | 2017 | 28098524 |
| recent h3n2 viruses have evolved specificity for extended, branched human-type receptors, conferring potential for increased avidity. | human and avian influenza viruses recognize different sialic acid-containing receptors, referred to as human-type (neuacα2-6gal) and avian-type (neuacα2-3gal), respectively. this presents a species barrier for aerosol droplet transmission of avian viruses in humans and ferrets. recent reports have suggested that current human h3n2 viruses no longer have strict specificity toward human-type receptors. using an influenza receptor glycan microarray with extended airway glycans, we find that h3n2 vi ... | 2017 | 28017661 |
| human monoclonal antibody 81.39a effectively neutralizes emerging influenza a viruses of group 1 and 2 hemagglutinins. | the pandemic threat posed by emerging zoonotic influenza a viruses necessitates development of antiviral agents effective against various antigenic subtypes. human monoclonal antibody (hmab) targeting the hemagglutinin (ha) stalk offers a promising approach to control influenza virus infections. here, we investigated the ability of the hmab 81.39a to inhibit in vitro replication of human and zoonotic viruses, representing 16 ha subtypes. the majority of viruses were effectively neutralized by 81 ... | 2016 | 27630240 |
| a defective interfering influenza rna inhibits infectious influenza virus replication in human respiratory tract cells: a potential new human antiviral. | defective interfering (di) viruses arise during the replication of influenza a virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. in this study we hypothesise that a cloned di influenza a virus rna may prevent infection of human respiratory epithelial cells with infection by influenza a. the di rna (244/pr8) was derived by a natural deletion process from segment 1 of influenza a/pr/8/34 (h1n1); it comprises 395 nucleotides a ... | 2016 | 27556481 |
| particle and subunit-based hemagglutinin vaccines provide protective efficacy against h1n1 influenza in pigs. | the increasing diversity of influenza strains circulating in swine herds escalates the potential for the emergence of novel pandemic viruses and highlights the need for swift development of new vaccines. baculovirus has proven to be a flexible platform for the generation of recombinant forms of hemagglutinin (ha) including subunit, vlp-displayed, and baculovirus-displayed antigens. these presentations have been shown to be efficacious in mouse, chicken, and ferret models but little is known abou ... | 2016 | 27374905 |
| flow cytometric and cytokine elispot approaches to characterize the cell-mediated immune response in ferrets following influenza virus infection. | influenza virus infections represent a significant socioeconomic and public health burden worldwide. although ferrets are considered by many to be ideal for modeling human responses to influenza infection and vaccination, efforts to understand the cellular immune response have been severely hampered by a paucity of standardized procedures and reagents. in this study, we developed flow cytometric and t cell enzyme-linked immunosorbent spot (elispot) approaches to characterize the leukocyte compos ... | 2016 | 27356897 |
| novel highly pathogenic avian a(h5n2) and a(h5n8) influenza viruses of clade 2.3.4.4 from north america have limited capacity for replication and transmission in mammals. | highly pathogenic influenza a(h5n8) viruses from clade 2.3.4.4 were introduced to north america by migratory birds in the fall of 2014. reassortment of a(h5n8) viruses with avian viruses of north american lineage resulted in the generation of novel a(h5n2) viruses with novel genotypes. through sequencing of recent avian influenza viruses, we identified pb1 and np gene segments very similar to those in the viruses isolated from north american waterfowl prior to the introduction of a(h5n8) to nort ... | 2017 | 27303732 |
| pandemic seasonal h1n1 reassortants recovered from patient material display a phenotype similar to that of the seasonal parent. | we have previously shown that 11 patients became naturally coinfected with seasonal h1n1 (a/h1n1) and pandemic h1n1 (pdm/h1n1) during the southern hemisphere winter of 2009 in new zealand. reassortment of influenza a viruses is readily observed during coinfection of host animals and in vitro; however, reports of reassortment occurring naturally in humans are rare. using clinical specimen material, we show reassortment between the two coinfecting viruses occurred with high likelihood directly in ... | 2016 | 27279619 |
| association between hemagglutinin stem-reactive antibodies and influenza a/h1n1 virus infection during the 2009 pandemic. | the discovery of influenza virus broadly neutralizing (brn) antibodies prompted efforts to develop universal vaccines. influenza virus stem-reactive (sr) broadly neutralizing antibodies have been detected by screening antibody phage display libraries. however, studies of sr brn antibodies in human serum, and their association with natural infection, are limited. to address this, pre- and postpandemic sera from a prospective community cohort study in vietnam were assessed for antibodies that inhi ... | 2016 | 27170747 |
| molecular requirements for a pandemic influenza virus: an acid-stable hemagglutinin protein. | influenza pandemics require that a virus containing a hemagglutinin (ha) surface antigen previously unseen by a majority of the population becomes airborne-transmissible between humans. although the ha protein is central to the emergence of a pandemic influenza virus, its required molecular properties for sustained transmission between humans are poorly defined. during virus entry, the ha protein binds receptors and is triggered by low ph in the endosome to cause membrane fusion; during egress, ... | 2016 | 26811446 |
| 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 ... | 2015 | 26719259 |
| prevalence, genetics, and transmissibility in ferrets of eurasian avian-like h1n1 swine influenza viruses. | pigs are important intermediate hosts for generating novel influenza viruses. the eurasian avian-like h1n1 (eah1n1) swine influenza viruses (sivs) have circulated in pigs since 1979, and human cases associated with eah1n1 sivs have been reported in several countries. however, the biologic properties of eah1n1 sivs are largely unknown. here, we performed extensive influenza surveillance in pigs in china and isolated 228 influenza viruses from 36,417 pigs. we found that 139 of the 228 strains from ... | 2016 | 26711995 |
| supplementation of h1n1pdm09 split vaccine with heterologous tandem repeat m2e5x virus-like particles confers improved cross-protection in ferrets. | current influenza vaccines induce strain-specific immunity to the highly variable hemagglutinin (ha) protein. it is therefore a high priority to develop vaccines that induce broadly cross-protective immunity to different strains of influenza. since influenza a m2 proteins are highly conserved among different strains, five tandem repeats of the extracellular peptide of m2 in a membrane-anchored form on virus-like particles (vlps) have been suggested to be a promising candidate for universal influ ... | 2016 | 26709639 |
| 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 ... | 2016 | 26657023 |
| evaluation of the attenuation, immunogenicity, and efficacy of a live virus vaccine generated by codon-pair bias de-optimization of the 2009 pandemic h1n1 influenza virus, in ferrets. | codon-pair bias de-optimization (cpbd) of viruses involves re-writing viral genes using statistically underrepresented codon pairs, without any changes to the amino acid sequence or codon usage. previously, this technology has been used to attenuate the influenza a/puerto rico/8/34 (h1n1) virus. the de-optimized virus was immunogenic and protected inbred mice from challenge. in order to assess whether cpbd could be used to produce a live vaccine against a clinically relevant influenza virus, we ... | 2016 | 26655630 |
| 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 ... | 2015 | 26559834 |
| nonreplicating influenza a virus vaccines confer broad protection against lethal challenge. | new vaccine technologies are being investigated for their ability to elicit broadly cross-protective immunity against a range of influenza viruses. we compared the efficacies of two intranasally delivered nonreplicating influenza virus vaccines (h1 and h5 s-flu) that are based on the suppression of the hemagglutinin signal sequence, with the corresponding h1n1 and h5n1 cold-adapted (ca) live attenuated influenza virus vaccines in mice and ferrets. administration of two doses of h1 or h5 s-flu va ... | 2015 | 26489862 |
| induction of broad-based immunity and protective efficacy by self-amplifying mrna vaccines encoding influenza virus hemagglutinin. | seasonal influenza is a vaccine-preventable disease that remains a major health problem worldwide, especially in immunocompromised populations. the impact of influenza disease is even greater when strains drift, and influenza pandemics can result when animal-derived influenza virus strains combine with seasonal strains. in this study, we used the sam technology and characterized the immunogenicity and efficacy of a self-amplifying mrna expressing influenza virus hemagglutinin (ha) antigen [sam(h ... | 2015 | 26468547 |
| the soft palate is an important site of adaptation for transmissible influenza viruses. | influenza a viruses pose a major public health threat by causing seasonal epidemics and sporadic pandemics. their epidemiological success relies on airborne transmission from person to person; however, the viral properties governing airborne transmission of influenza a viruses are complex. influenza a virus infection is mediated via binding of the viral haemagglutinin (ha) to terminally attached α2,3 or α2,6 sialic acids on cell surface glycoproteins. human influenza a viruses preferentially bin ... | 2015 | 26416728 |
| changes to the dynamic nature of hemagglutinin and the emergence of the 2009 pandemic h1n1 influenza virus. | the virologic factors that limit the transmission of swine influenza viruses between humans are unresolved. while it has been shown that acquisition of the neuraminidase (na) and matrix (m) gene segments from a eurasian-lineage swine virus was required for airborne transmission of the 2009 pandemic h1n1 virus (h1n1pdm09), we show here that an arginine to lysine change in the hemagglutinin (ha) was also necessary. this change at position 149 was distal to the receptor binding site but affected vi ... | 2015 | 26269288 |
| possible basis for the emergence of h1n1 viruses with pandemic potential from avian hosts. | influenza a viruses of the h1n1 subtype have emerged from the avian influenza gene pool in aquatic birds and caused human pandemics at least twice during the past century. despite this fact, surprisingly little is known about the h1n1 gene pool in the aquatic bird reservoir. a preliminary study showed that an h1n1 virus from a shorebird of the charadriiformes order was transmitted between animals through the airborne route of infection, whereas an h1n1 virus from a bird of the anseriformes order ... | 2015 | 26251829 |
| 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 ... | 2015 | 26079133 |
| correlation between the interval of influenza virus infectivity and results of diagnostic assays in a ferret model. | the relationship between influenza virus infectivity and virus shedding, based on different diagnostic methods, has not been defined. | 2016 | 26068783 |
| 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 ... | 2015 | 26063430 |
| 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 ... | 2015 | 26051886 |
| 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 ... | 2015 | 26022199 |
| 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 ... | 2015 | 25986634 |
| 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. | 2015 | 25943206 |
| 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 ... | 2015 | 25746201 |
| 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 ... | 2015 | 25746173 |
| 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 ... | 2015 | 25691635 |
| 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 ... | 2015 | 25609810 |
| 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 ... | 2014 | 25597188 |
| 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. ... | 2015 | 25555619 |
| 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 ... | 2014 | 25187553 |
| 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 ... | 2014 | 25163545 |
| 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 ... | 2014 | 25122786 |
| 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 ... | 2014 | 25100840 |
| 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 ... | 2014 | 25078114 |
| 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 ... | 2015 | 24977303 |
| 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 ... | 2014 | 24840623 |
| 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 ( ... | 2014 | 24699865 |
| 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 ... | 2014 | 24581932 |
| 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 ... | 2014 | 24511825 |
| 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 ... | 2014 | 24421115 |
| higher immunological protection of pandemic 2009 h1n1 influenza live virus infection than split vaccine against the homologous virus for long term immunization in ferret. | the study was to evaluate the long term immunological efficacy of pandemic 2009 h1n1 influenza live virus infection and split vaccine against the homologous virus challenge in ferrets. antibodies in ferrets were monitored by haemagglutination inhibition (hi) assay for 200 days, the hi titers of both infected-only and vaccinated plus infected ferrets could maintain a high level for at least 182 days, without significant difference between the two infected groups. while one-dose and two-dose vacci ... | 2012 | 24293813 |
| substitutions near the receptor binding site determine major antigenic change during influenza virus evolution. | the molecular basis of antigenic drift was determined for the hemagglutinin (ha) of human influenza a/h3n2 virus. from 1968 to 2003, antigenic change was caused mainly by single amino acid substitutions, which occurred at only seven positions in ha immediately adjacent to the receptor binding site. most of these substitutions were involved in antigenic change more than once. equivalent positions were responsible for the recent antigenic changes of influenza b and a/h1n1 viruses. substitution of ... | 2013 | 24264991 |
| 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 ... | 2014 | 24257597 |
| 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 ... | 2014 | 24131710 |
| emergence of h3n2pm-like and novel reassortant h3n1 swine viruses possessing segments derived from the a (h1n1)pdm09 influenza virus, korea. | human-to-swine transmission of the pandemic h1n1 2009 [a(h1n1)pdm09] virus in pig populations resulted in reassortment events with endemic swine influenza viruses worldwide. | 2013 | 24034626 |
| 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 ... | 2014 | 23990570 |
| the homologous tripartite viral rna polymerase of a/swine/korea/ct1204/2009(h1n2) influenza virus synergistically drives efficient replication and promotes respiratory droplet transmission in ferrets. | we previously reported that influenza a/swine/korea/1204/2009(h1n2) virus was virulent and transmissible in ferrets in which the respiratory-droplet-transmissible virus (ct-sw/1204) had acquired simultaneous hemagglutinin (had225g) and neuraminidase (nas315n) mutations. incorporating these mutations into the nonpathogenic a/swine/korea/1130/2009(h1n2, sw/1130) virus consequently altered pathogenicity and growth in animal models but could not establish efficient transmission or noticeable disease ... | 2013 | 23864624 |
| 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 ... | 2013 | 23864615 |
| characterization of h7n9 influenza a viruses isolated from humans. | avian influenza a viruses rarely infect humans; however, when human infection and subsequent human-to-human transmission occurs, worldwide outbreaks (pandemics) can result. the recent sporadic infections of humans in china with a previously unrecognized avian influenza a virus of the h7n9 subtype (a(h7n9)) have caused concern owing to the appreciable case fatality rate associated with these infections (more than 25%), potential instances of human-to-human transmission, and the lack of pre-existi ... | 2013 | 23842494 |
| asparagine substitution at pb2 residue 701 enhances the replication, pathogenicity, and transmission of the 2009 pandemic h1n1 influenza a virus. | the 2009/2010 pandemic influenza virus (h1n1pdm) contains an avian-lineage pb2 gene that lacks e627k and d701n substitutions important in the pathogenesis and transmission of avian-origin viruses in humans or other mammals. previous studies have shown that pb2-627k is not necessary because of a compensatory q591r substitution. the role that pb2-701n plays in the h1n1pdm phenotype is not well understood. therefore, pb2-d701n was introduced into an h1n1pdm virus (a/new york/1682/2009 (ny1682)) and ... | 2013 | 23799150 |
| intranasal antibody gene transfer in mice and ferrets elicits broad protection against pandemic influenza. | the emergence of a new influenza pandemic remains a threat that could result in a substantial loss of life and economic disruption worldwide. advances in human antibody isolation have led to the discovery of monoclonal antibodies (mabs) that have broad neutralizing activity against various influenza strains, although their direct use for prophylaxis is impractical. to overcome this limitation, our approach is to deliver antibody via adeno-associated virus (aav) vectors to the site of initial inf ... | 2013 | 23720583 |
| glycosylations in the globular head of the hemagglutinin protein modulate the virulence and antigenic properties of the h1n1 influenza viruses. | with the global spread of the 2009 pandemic h1n1 (ph1n1) influenza virus, there are increasing worries about evolution through antigenic drift. one way previous seasonal h1n1 and h3n2 influenza strains have evolved over time is by acquiring additional glycosylations in the globular head of their hemagglutinin (ha) proteins; these glycosylations have been believed to shield antigenically relevant regions from antibody immune responses. we added additional ha glycosylation sites to influenza a/net ... | 2013 | 23720581 |
| prolonged influenza virus shedding and emergence of antiviral resistance in immunocompromised patients and ferrets. | immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients. little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients. among all 189 influenza a virus infected immunocompromised patients admitted to erasmusmc, 71 were hospitalized, since the start of the 2009 h1n1 pandemic. we identified 11 (15%) cases with prolonged 2009 pandemic virus replication (longer than 14 days), ... | 2013 | 23717200 |
| intranasal vaccination with h5, h7 and h9 hemagglutinins co-localized in a virus-like particle protects ferrets from multiple avian influenza viruses. | avian influenza h5, h7 and h9 viruses top the world health organization's (who) list of subtypes with the greatest pandemic potential. here we describe a recombinant virus-like particle (vlp) that co-localizes hemagglutinin (ha) proteins derived from h5n1, h7n2, and h9n2 viruses as an experimental vaccine against these viruses. a baculovirus vector was configured to co-express the h5, h7, and h9 genes from a/viet nam/1203/2004 (h5n1), a/new york/107/2003 (h7n2) and a/hong kong/33982/2009 (h9n2) ... | 2013 | 23618102 |
| immunity toward h1n1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure. | evolution of h1n1 influenza a outbreaks of the past 100 years is interesting and significantly complex and details of h1n1 genetic drift remains unknown. here we investigated the clinical characteristics and immune cross-reactivity of significant historical h1n1 strains. we infected ferrets with h1n1 strains from 1943, 1947, 1977, 1986, 1999, and 2009 and showed each produced a unique clinical signature. we found significant cross-reactivity between viruses with similar ha sequences. interesting ... | 2013 | 23608887 |