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hepeviridae: an expanding family of vertebrate viruses.the hepatitis e virus (hev) was first identified in 1990, although hepatitis e-like diseases in humans have been recorded for a long time dating back to the 18th century. the hev genotypes 1-4 have been subsequently detected in human hepatitis e cases with different geographical distribution and different modes of transmission. genotypes 3 and 4 have been identified in parallel in pigs, wild boars and other animal species and their zoonotic potential has been confirmed. until 2010, these genotyp ...201425050488
consensus proposals for classification of the family hepeviridae.the family hepeviridae consists of positive-stranded rna viruses that infect a wide range of mammalian species, as well as chickens and trout. a subset of these viruses infects humans and can cause a self-limiting acute hepatitis that may become chronic in immunosuppressed individuals. current published descriptions of the taxonomical divisions within the family hepeviridae are contradictory in relation to the assignment of species and genotypes. through analysis of existing sequence information ...201424989172
complete genome of hepatitis e virus from laboratory ferrets.the complete genome of hepatitis e virus (hev) from laboratory ferrets imported from the united states was identified. this virus shared only 82.4%-82.5% nt sequence identities with strains from the netherlands, which indicated that the ferret hev genome is genetically diverse. some laboratory ferrets were contaminated with hev.201424655541
molecular characterization of a novel hepatitis e virus (hev) strain obtained from a wild boar in japan that is highly divergent from the previously recognized hev strains.although a consensus classification system for hepatitis e virus (hev) genotypes is currently unavailable, hev variants (jboar135-shiz09 and wbjoy_06) from wild boars (sus scrofa leucomystax) have provisionally been classified into two novel genotypes (5 and 6). while performing a survey of hev infections among 566 wild boars that were captured in japan between january 2010 and august 2013, we found 24 boars (4.2%) with ongoing hev infections: 13 had genotype 3 hev, 10 had genotype 4 hev and the ...201424370869
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
hemozoin is a potent adjuvant for hemagglutinin split vaccine without pyrogenicity in ferrets.synthetic hemozoin (shz, also known as β-hematin) from monomeric heme is a particle adjuvant which activates antigen-presenting cells (apcs), such as dendritic cells and macrophages, and enhances humoral immune responses to several antigens, including ovalbumin, human serum albumin, and serine repeat antigen 36 of plasmodium falciparum. in the present study, we evaluated the adjuvanticity and pyrogenicity of shz as an adjuvant for seasonal trivalent hemagglutinin split vaccine (sv) for humans us ...201424721532
rabies and rabies virus in wildlife in mainland china, 1990-2013.the number of wildlife rabies and wildlife-associated human and livestock rabies cases has increased in recent years, particularly in the southeast and northeast regions of mainland china. to better understand wildlife rabies and its role in human and livestock rabies, we reviewed what is known about wildlife rabies from the 1990s to 2013 in mainland china. in addition, the genetic diversity and phylogeny of available wildlife-originated rabies viruses (rabvs) were analyzed. several wildlife spe ...201424911887
[sequencing and analysis of n gene of street rabies virus isolated from different hosts in zhejiang province].to elucidate the characteristics of genetic variability and its relationship with prevalence, through sequencing and analysis of n gene among street rabies virus isolated from different hosts (homo sapiens, ferret badger, dog) in zhejiang province.201425294078
molecular characterization of cryptically circulating rabies virus from ferret badgers, taiwan.after the last reported cases of rabies in a human in 1959 and a nonhuman animal in 1961, taiwan was considered free from rabies. however, during 2012-2013, an outbreak occurred among ferret badgers in taiwan. to examine the origin of this virus strain, we sequenced 3 complete genomes and acquired multiple rabies virus (rabv) nucleoprotein and glycoprotein sequences. phylogeographic analyses demonstrated that the rabv affecting the taiwan ferret badgers (rabv-twfb) is a distinct lineage within t ...201424751120
molecular characterization of three ferret badger (melogale moschata) rabies virus isolates from jiangxi province, china.ferret badger (fb) rabies viruses jx09-17(fb), jx09-18 and jx10-37 were isolated from three different regions in jiangxi province, china, in 2009 and 2010. the complete nucleotide sequence identity between these three isolates was 87-93 %. compared with the other chinese rabies virus isolates and vaccine strains, 101 substitutions (53 in jx10-37, 23 in jx09-17(fb) and 25 in jx09-18) in the five structural proteins were observed, and 47 of these substitutions (27 in jx10-37, 14 in jx09-17(fb) and ...201424643334
gall bladder rupture associated with cholecystitis in a domestic ferret (mustela putorius).a six-year-old neutered female albino ferret was presented with an acute episode of lethargy and anorexia. clinical examination revealed marked cranial abdominal pain. a severe neutrophilic leukocytosis was present. abdominal ultrasound was consistent with a diffuse peritonitis and severe bile duct inflammation. cytology of the abdominal effusion revealed bile peritonitis. an exploratory laparotomy was performed and the gall bladder appeared inflamed with multiple perforations. a cholecystectomy ...201425168742
lung phenotype of juvenile and adult cystic fibrosis transmembrane conductance regulator-knockout ferrets.chronic bacterial lung infections in cystic fibrosis (cf) are caused by defects in the cf transmembrane conductance regulator chloride channel. previously, we described that newborn cf transmembrane conductance regulator-knockout ferrets rapidly develop lung infections within the first week of life. here, we report a more slowly progressing lung bacterial colonization phenotype observed in juvenile to adult cf ferrets reared on a layered antibiotic regimen. even on antibiotics, cf ferrets were s ...201424074402
gastrointestinal pathology in juvenile and adult cftr-knockout ferrets.cystic fibrosis (cf) is a multiorgan disease caused by loss of a functional cystic fibrosis transmembrane conductance regulator (cftr) chloride channel in many epithelia of the body. here we report the pathology observed in the gastrointestinal organs of juvenile to adult cftr-knockout ferrets. cf gastrointestinal manifestations included gastric ulceration, intestinal bacterial overgrowth with villous atrophy, and rectal prolapse. metagenomic phylogenetic analysis of fecal microbiota by deep seq ...201424637292
the spectral transmission of ocular media suggests ultraviolet sensitivity is widespread among mammals.although ultraviolet (uv) sensitivity is widespread among animals it is considered rare in mammals, being restricted to the few species that have a visual pigment maximally sensitive (λmax) below 400 nm. however, even animals without such a pigment will be uv-sensitive if they have ocular media that transmit these wavelengths, as all visual pigments absorb significant amounts of uv if the energy level is sufficient. although it is known that lenses of diurnal sciurid rodents, tree shrews and pri ...201424552839
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
h5 n-terminal β sheet promotes oligomerization of h7-ha1 that induces better antibody affinity maturation and enhanced protection against h7n7 and h7n9 viruses compared to inactivated influenza vaccine.initiation of mass vaccination is critical in response to influenza pandemic. there is an urgent need of a simple, rapid method for production of influenza vaccine that is more effective than current traditional influenza vaccines. recent h7n9 transmissions to humans in china with high morbidity/mortality initiated extensive vaccine evaluation. we produced the ha1 domains (amino acids 1-320) from h7n9 and h7n7 strains in e. coli. both were found to contain primarily monomers/trimers with low oli ...201425284811
feline immunodeficiency virus envelope glycoproteins antagonize tetherin through a distinctive mechanism that requires virion incorporation.bst2/tetherin inhibits the release of enveloped viruses from cells. primate lentiviruses have evolved specific antagonists (vpu, nef, and env). here we characterized tetherin proteins of species representing both branches of the order carnivora. comparison of tiger and cat (feliformia) to dog and ferret (caniformia) genes demonstrated that the tiger and cat share a start codon mutation that truncated most of the tetherin cytoplasmic tail early in the feliformia lineage (19 of 27 amino acids, inc ...201424390322
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
corynebacterium ulcerans in ferrets. 201424377676
experimental oral immunization of ferret badgers (melogale moschata) with a recombinant canine adenovirus vaccine cav-2-e3δ-rgp and an attenuated rabies virus srv9.ferret badgers (melogale moschata) are a major reservoir of rabies virus in southeastern china. oral immunization has been shown to be a practical method for wildlife rabies management in europe and north america. two groups of 20 ferret badgers were given a single oral dose of a recombinant canine adenovirus-rabies vaccine, cav-2-e3δ-rgp, or an experimental attenuated rabies virus vaccine, srv9. at 21 days, all ferret badgers had seroconverted, with serum virus-neutralizing antibodies ranging f ...201424506428
an orally available, small-molecule polymerase inhibitor shows efficacy against a lethal morbillivirus infection in a large animal model.measles virus is a highly infectious morbillivirus responsible for major morbidity and mortality in unvaccinated humans. the related, zoonotic canine distemper virus (cdv) induces morbillivirus disease in ferrets with 100% lethality. we report an orally available, shelf-stable pan-morbillivirus inhibitor that targets the viral rna polymerase. prophylactic oral treatment of ferrets infected intranasally with a lethal cdv dose reduced viremia and prolonged survival. ferrets infected with the same ...201424739760
using the ferret model to study morbillivirus entry, spread, transmission and cross-species infection.canine distemper virus (cdv) is an animal morbillivirus with a worldwide circulation that infects carnivores, including domestic dogs and an assortment of wildlife hosts. the development of reverse genetics systems for wild-type strains of cdv and the use of the resulting recombinant (r) viruses to infect ferrets by a natural route has shed new light on the temporal pathogenesis of distemper. combining fluorescent protein expressing recombinant viruses and multimodal, macroscopic and microscopic ...201424525290
wildlife reservoirs of canine distemper virus resulted in a major outbreak in danish farmed mink (neovison vison).a major outbreak of canine distemper virus (cdv) in danish farmed mink (neovison vison) started in the late summer period of 2012. at the same time, a high number of diseased and dead wildlife species such as foxes, raccoon dogs, and ferrets were observed. to track the origin of the outbreak virus full-length sequencing of the receptor binding surface protein hemagglutinin (h) was performed on 26 cdv's collected from mink and 10 cdv's collected from wildlife species. subsequent phylogenetic anal ...201424454897
morbillivirus control of the interferon response: relevance of stat2 and mda5 but not stat1 for canine distemper virus virulence in ferrets.the v proteins of paramyxoviruses control the innate immune response. in particular, the v protein of the genus morbillivirus interferes with the signal transducer and activator of transcription 1 (stat1), stat2, and melanoma differentiation-associated protein 5 (mda5) signaling pathways. to characterize the contributions of these pathways to canine distemper virus (cdv) pathogenesis, we took advantage of the knowledge about the mechanisms of interaction between the measles virus v protein with ...201424371065
occurrence and molecular typing of giardia isolates in pet rabbits, chinchillas, guinea pigs and ferrets collected in europe during 2006-2012.a total of 1180 faecal samples (528 from rabbits, 531 from chinchillas and 121 from guinea pigs) collected during 2006-2012 by veterinarians in germany and in other european countries were submitted to a diagnostic laboratory for giardia testing by means of coproantigen elisa. of these samples, 40 rabbits (7.6 per cent), 326 chinchillas (61.4 per cent) and five guinea pigs (4.1 per cent ) were found to be positive. to gain insights into the genetic identity of giardia in small mammals, elisa-pos ...201424696441
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
influenza virus infectivity and virulence following ocular-only aerosol inoculation of ferrets.respiratory pathogens have traditionally been studied by examining the exposure and infection of respiratory tract tissues. however, these studies typically overlook the role of ocular surfaces, which represent both a potential site of virus replication and a portal of entry for the establishment of a respiratory infection. to model transocular virus entry in a mammalian species, we established a novel inoculation method that delivers an aerosol inoculum exclusively to the ferret ocular surface. ...201424920819
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
influenza h1n1pdm-specific maternal antibodies offer limited protection against wild-type virus replication and influence influenza vaccination in ferrets.the objective was to study passively acquired influenza h1n1 pandemic (h1n1pdm) maternal antibody kinetics and its impact on subsequent influenza infection and vaccination in ferrets during an outbreak of the h1n1pdm.201424734293
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
intranasally administered endocine formulated 2009 pandemic influenza h1n1 vaccine induces broad specific antibody responses and confers protection in ferrets.influenza is a contagious respiratory disease caused by an influenza virus. due to continuous antigenic drift of seasonal influenza viruses, influenza vaccines need to be adjusted before every influenza season. this allows annual vaccination with multivalent seasonal influenza vaccines, recommended especially for high-risk groups. there is a need for a seasonal influenza vaccine that induces broader and longer lasting protection upon easy administration. endocine is a lipid-based mucosal adjuvan ...201424690149
mammalian pathogenesis of oseltamivir-resistant pandemic (h1n1) 2009 influenza virus isolated in south korea.oseltamivir, a neuraminidase (na) inhibitor, has been widely used for the treatment of patients infected with the pandemic (h1n1) 2009 influenza virus. with the increasing use of oseltamivir, drug-resistant mutants emerged rapidly and 11 cases of resistant viruses were detected during the 2009 h1n1 pandemic in south korea. to better understand the differences between oseltamivir-susceptible and oseltamivir-resistant virus, we compared the replication and pathogenesis of the na h275y mutant virus ...201424657788
humans and ferrets with prior h1n1 influenza virus infections do not exhibit evidence of original antigenic sin after infection or vaccination with the 2009 pandemic h1n1 influenza virus.the hypothesis of original antigenic sin (oas) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. the purpose of our study was to seek evidence of oas after infection or vaccination with the 2009 pandemic h1n1 (2009 ph1n1) virus in ferrets and human ...201424648486
protection of ferrets from pulmonary injury due to h1n1 2009 influenza virus infection: immunopathology tractable by sphingosine-1-phosphate 1 receptor agonist therapy.influenza infection of humans remains an important public health problem. vaccine strategies result in a significant but only partial control (65-85%) of infection. thus, chemotherapeutic approaches are needed to provide a solution both for vaccine failures and to limit infection in the unvaccinated population. previously (walsh et al., 2011; teijaro et al., 2011) documented that sphingosine-1-phosphate 1 receptor (s1p1r) agonists significantly protected mice against pathogenic h1n1 influenza vi ...201424606692
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
randomized controlled ferret study to assess the direct impact of 2008-09 trivalent inactivated influenza vaccine on a(h1n1)pdm09 disease risk.during spring-summer 2009, several observational studies from canada showed increased risk of medically-attended, laboratory-confirmed a(h1n1)pdm09 illness among prior recipients of 2008-09 trivalent inactivated influenza vaccine (tiv). explanatory hypotheses included direct and indirect vaccine effects. in a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008-09 tiv may have directly influenced a(h1n1)pdm09 illness. thirty-two ferrets (16/group) received 0.5 ml i ...201424475142
vaccination of monoglycosylated hemagglutinin induces cross-strain protection against influenza virus infections.the 2009 h1n1 pandemic and recent human cases of h5n1, h7n9, and h6n1 in asia highlight the need for a universal influenza vaccine that can provide cross-strain or even cross-subtype protection. here, we show that recombinant monoglycosylated hemagglutinin (hamg) with an intact protein structure from either seasonal or pandemic h1n1 can be used as a vaccine for cross-strain protection against various h1n1 viruses in circulation from 1933 to 2009 in mice and ferrets. in the hamg vaccine, highly c ...201424469815
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
assessment of influenza virus hemagglutinin stalk-based immunity in ferrets.therapeutic monoclonal antibodies that target the conserved stalk domain of the influenza virus hemagglutinin and stalk-based universal influenza virus vaccine strategies are being developed as promising countermeasures for influenza virus infections. the pan-h1-reactive monoclonal antibody 6f12 has been extensively characterized and shows broad efficacy against divergent h1n1 strains in the mouse model. here we demonstrate its efficacy against a pandemic h1n1 challenge virus in the ferret model ...201424403585
a single amino acid in the stalk region of the h1n1pdm influenza virus ha protein affects viral fusion, stability and infectivity.the 2009 h1n1 pandemic (h1n1pdm) viruses have evolved to contain an e47k substitution in the ha2 subunit of the stalk region of the hemagglutinin (ha) protein. the biological significance of this single amino acid change was investigated by comparing a/california/7/2009 (ha2-e47) with a later strain, a/brisbane/10/2010 (ha2-k47). the e47k change was found to reduce the threshold ph for membrane fusion from 5.4 to 5.0. an inter-monomer salt bridge between k47 in ha2 and e21 in ha1, a neighboring ...201424391498
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
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
polymerase discordance in novel swine influenza h3n2v constellations is tolerated in swine but not human respiratory epithelial cells.swine-origin h3n2v, a variant of h3n2 influenza virus, is a concern for novel reassortment with circulating pandemic h1n1 influenza virus (h1n1pdm09) in swine because this can lead to the emergence of a novel pandemic virus. in this study, the reassortment prevalence of h3n2v with h1n1pdm09 was determined in swine cells. reassortants evaluated showed that the h1n1pdm09 polymerase (pa) segment occurred within swine h3n2 with ∼ 80% frequency. the swine h3n2-human h1n1pdm09 pa reassortant (swh3n2-h ...201425330303
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
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
influenza vaccination accelerates recovery of ferrets from lymphopenia.ferrets are a useful animal model for human influenza virus infections, since they closely mimic the pathogenesis of influenza viruses observed in humans. however, a lack of reagents, especially for flow cytometry of immune cell subsets, has limited research in this model. here we use a panel of primarily species cross-reactive antibodies to identify ferret t cells, cytotoxic t lymphocytes (ctl), b cells, and granulocytes in peripheral blood. following infection with seasonal h3n2 or h1n1pdm09 i ...201424968319
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
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
evaluation of three live attenuated h2 pandemic influenza vaccine candidates in mice and ferrets.h2 influenza viruses have not circulated in humans since 1968, and therefore a significant portion of the population would be susceptible to infection should h2 influenza viruses reemerge. h2 influenza viruses continue to circulate in avian reservoirs worldwide, and these reservoirs are a potential source from which these viruses could emerge. three reassortant cold-adapted (ca) h2 pandemic influenza vaccine candidates with hemagglutinin (ha) and neuraminidase (na) genes derived from the wild-ty ...201424371061
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
dna prime and virus-like particle boost from a single h5n1 strain elicits broadly neutralizing antibody responses against head region of h5 hemagglutinin.since 1996, highly pathogenic avian influenza (hpai) h5n1 virus has presented a persistent threat to public health. its high degree of genetic diversity also poses enormous challenges in developing effective vaccines. to search for vaccine regimens that could elicit broadly neutralizing antibody responses against diverse hpai h5n1 strains, in the present study we tested h5 hemagglutinin (ha) from an a/thailand/1(kan)-1/2004 strain in a heterologous prime-boost vaccination. we demonstrated that p ...201423911711
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
human h7n9 and h5n1 influenza viruses differ in induction of cytokines and tissue tropism.since emerging in 2013, the avian-origin h7n9 influenza viruses have resulted in over 400 human infections, leading to 115 deaths to date. although the epidemiology differs from human highly pathogenic avian h5n1 influenza virus infections, there is a similar rapid progression to acute respiratory distress syndrome. the aim of these studies was to compare the pathological and immunological characteristics of a panel of human h7n9 and h5n1 viruses in vitro and in vivo. although there were similar ...201425210188
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
antigenic variation of clade 2.1 h5n1 virus is determined by a few amino acid substitutions immediately adjacent to the receptor binding site.highly pathogenic avian influenza (hpai) viruses of the h5n1 subtype are genetically highly variable and have diversified into multiple phylogenetic clades over the past decade. antigenic drift is a well-studied phenomenon for seasonal human influenza viruses, but much less is known about the antigenic evolution of hpai h5n1 viruses that circulate in poultry. in this study, we focused on hpai h5n1 viruses that are enzootic to indonesia. we selected representative viruses from genetically distinc ...201424917596
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
activation of coagulation and tissue fibrin deposition in experimental influenza in ferrets.epidemiological studies relate influenza infection with vascular diseases like myocardial infarction. the hypothesis that influenza infection has procoagulant effects on humans has been investigated by experimental animal models. however, these studies often made use of animal models only susceptible to adapted influenza viruses (mouse adapted influenza strains) or remained inconclusive. therefore, we decided to study the influence of infection with human influenza virus isolates on coagulation ...201424884666
intranasal h5n1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.we investigated the protective efficacy of two intranasal chitosan (csn and tm-csn) adjuvanted h5n1 influenza vaccines against highly pathogenic avian influenza (hpai) intratracheal and intranasal challenge in a ferret model. six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, csn adjuvanted antigen, or tm-csn adjuvanted antigen. homologous and intra-subtypic antibody cross-reacting responses were assessed. ferrets were inoculated intrat ...201424850536
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
red ginseng-containing diet helps to protect mice and ferrets from the lethal infection by highly pathogenic h5n1 influenza virus.the highly pathogenic (hp) h5n1 influenza virus is endemic in many countries and has a great potential for a pandemic in humans. the immune-enhancing prowess of ginseng has been known for millennia. we aimed to study whether mice and ferrets fed with red ginseng could be better protected from the lethal infections of hp h5n1 influenza virus than the infected unfed mice and ferrets. we fed mice and ferrets with red ginseng prior to when they were infected with hp h5n1 influenza virus. the mice an ...201424558309
gla-af, an emulsion-free vaccine adjuvant for pandemic influenza.the ongoing threat from influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. currently, the most successful adjuvants for influenza vaccines are squalene-based oil-in-water emulsions. these adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manuf ...201424551202
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
structural basis for a switch in receptor binding specificity of two h5n1 hemagglutinin mutants.avian h5n1 influenza viruses continue to spread in wild birds and domestic poultry with sporadic infection in humans. receptor binding specificity changes are a prerequisite for h5n1 viruses and other zoonotic viruses to be transmitted among humans. previous reported hemagglutinin (ha) mutants from ferret-transmissible h5n1 viruses of a/vietnam/1203/2004 and a/indonesia/5/2005 showed slightly increased, but still very weak, binding to human receptors. from mutagenesis and glycan array studies, w ...201526586437
matrix-m adjuvated seasonal virosomal influenza vaccine induces partial protection in mice and ferrets against avian h5 and h7 challenge.there is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. it is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. in addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. an effective pre-pandemic vaccine is therefore required as a fir ...201526402787
hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection.the antibody response to influenza is primarily focused on the head region of the hemagglutinin (ha) glycoprotein, which in turn undergoes antigenic drift, thus necessitating annual updates of influenza vaccines. in contrast, the immunogenically subdominant stem region of ha is highly conserved and recognized by antibodies capable of binding multiple ha subtypes. here we report the structure-based development of an h1 ha stem-only immunogen that confers heterosubtypic protection in mice and ferr ...201526301691
detection and characterization of clade 1 reassortant h5n1 viruses isolated from human cases in vietnam during 2013.highly pathogenic avian influenza (hpai) h5n1 is endemic in vietnamese poultry and has caused sporadic human infection in vietnam since 2003. human infections with hpai h5n1 are of concern due to a high mortality rate and the potential for the emergence of pandemic viruses with sustained human-to-human transmission. viruses isolated from humans in southern vietnam have been classified as clade 1 with a single genome constellation (vn3) since their earliest detection in 2003. this is consistent w ...201526244768
fitness inference from short-read data: within-host evolution of a reassortant h5n1 influenza virus.we present a method to infer the role of selection acting during the within-host evolution of the influenza virus from short-read genome sequence data. linkage disequilibrium between loci is accounted for by treating short-read sequences as noisy multilocus emissions from an underlying model of haplotype evolution. a hierarchical model-selection procedure is used to infer the underlying fitness landscape of the virus insofar as that landscape is explored by the viral population. in a first appli ...201526243288
matrix m h5n1 vaccine induces cross-h5 clade humoral immune responses in a randomized clinical trial and provides protection from highly pathogenic influenza challenge in ferrets.highly pathogenic avian influenza (hpai) viruses constitute a pandemic threat and the development of effective vaccines is a global priority. sixty adults were recruited into a randomized clinical trial and were intramuscularly immunized with two virosomal vaccine h5n1 (nibrg-14) doses (21 days apart) of 30 μg ha alone or 1.5, 7.5 or 30 μg ha adjuvanted with matrix m. the kinetics and longevity of the serological responses against nibrg-14 were determined by haemagglutination inhibition (hi), si ...201526147369
assessment of transmission, pathogenesis and adaptation of h2 subtype influenza viruses in ferrets.after their disappearance from the human population in 1968, influenza h2 viruses have continued to circulate in the natural avian reservoir. the isolation of this virus subtype from multiple bird species as well as swine highlights the need to better understand the potential of these viruses to spread and cause disease in humans. here we analyzed the virulence, transmissibility and receptor-binding preference of two avian influenza h2 viruses (h2n2 and h2n3) and compared them to a swine h2n3 (a ...201525659818
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 live attenuated vaccine prevents replication and transmission of h7n9 virus in mammals.the continued spread of the newly emerged h7n9 viruses among poultry in china, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. an mf59-adjuvant h7n9 inactivated vaccine is reported to be well-tolerated and immunogenic in humans; however a study in ferrets indicated that while a single dose of the inactivated h7n9 vaccine reduced disease severity, it did not prevent virus replication a ...201526058711
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
h3n2 mismatch of 2014-15 northern hemisphere influenza vaccines and head-to-head comparison between human and ferret antisera derived antigenic maps.the poor performance of 2014-15 northern hemisphere (nh) influenza vaccines was attributed to mismatched h3n2 component with circulating epidemic strains. using human serum samples collected from 2009-10, 2010-11 and 2014-15 nh influenza vaccine trials, we assessed their cross-reactive hemagglutination inhibition (hai) antibody responses against recent h3 epidemic isolates. all three populations (children, adults, and older adults) vaccinated with the 2014-15 nh egg- or cell-based vaccine, showe ...201526472175
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
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
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
hemagglutinin stalk immunity reduces influenza virus replication and transmission in ferrets.we assessed whether influenza virus hemagglutinin stalk-based immunity protects ferrets against aerosol-transmitted h1n1 influenza virus infection. immunization of ferrets by a universal influenza virus vaccine strategy based on viral vectors expressing chimeric hemagglutinin constructs induced stalk-specific antibody responses. stalk-immunized ferrets were cohoused with h1n1-infected ferrets under conditions that permitted virus transmission. hemagglutinin stalk-immunized ferrets had lower vira ...201526719251
complete genome sequence of the type strain corynebacterium mustelae dsm 45274, isolated from various tissues of a male ferret with lethal sepsis.the complete genome of corynebacterium mustelae dsm 45274 comprises 3,474,226 bp and 3,188 genes. prominent niche and virulence factors are spabca- and spadef-type pili with similarity to pilus proteins of corynebacterium resistens and corynebacterium urealyticum and an immunomodulatory endos-like endoglycosidase probably catalyzing the removal of distinct glycans from igg antibodies.201526358597
canine rotavirus c strain detected in hungary shows marked genotype diversity.species c rotaviruses (rvc) have been identified in humans and animals, including pigs, cows and ferrets. in dogs, rvc strains have been reported anecdotally on the basis of visualization of rotavirus-like virions by electron microscopy combined with specific electrophoretic migration patterns of the genomic rna segments. however, no further molecular characterization of these viruses was performed. here, we report the detection of a canine rvc in the stool of a dog with enteritis. analysis of t ...201526297005
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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