Publications

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 ...	2015	25659818
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/ ...	2015	25444799
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 ...	2015	25410860
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
plant-derived h7 vlp vaccine elicits protective immune response against h7n9 influenza virus in mice and ferrets.	in march 2013, the chinese centre for disease control and prevention confirmed the first reported case of human infection with an avian influenza a h7n9 virus. infection with this virus often caused severe pneumonia and acute respiratory distress syndrome resulting in a case fatality rate >35%. the risk of pandemic highlighted, once again, the need for a more rapid and scalable vaccine response capability. here, we describe the rapid (19 days) development of a plant-derived vlp vaccine based on ...	2015	26432915
dual e627k and d701n mutations in the pb2 protein of a(h7n9) influenza virus increased its virulence in mammalian models.	the ongoing avian h7n9 influenza outbreaks in china have caused significant human fatal cases and the virus is becoming established in poultry. mutations with potential to increase mammalian adaptation have occurred in the polymerase basic protein 2 (pb2) and other viral genes. here we found that dual 627k and 701n mutations could readily occur during transmission of the virus among ferrets via direct physical contact, and these mutations conferred higher polymerase activity and improved viral r ...	2015	26391278
recombinant h7 hemagglutinin forms subviral particles that protect mice and ferrets from challenge with h7n9 influenza virus.	a novel avian-origin influenza a h7n9 virus emerged in china in 2013 and continues to cause sporadic human infections with mortality rates approaching 35%. currently there are no approved human vaccines for h7n9 virus. recombinant approaches including hemagglutinin (ha) and virus-like particles (vlps) have resulted in experimental vaccines with advantageous safety and manufacturing characteristics. while high immunogenicity of vlp vaccines has been attributed to the native conformation of ha arr ...	2015	26207590
development of influenza a(h7n9) candidate vaccine viruses with improved hemagglutinin antigen yield in eggs.	the emergence of avian influenza a(h7n9) virus in poultry causing zoonotic human infections was reported on march 31, 2013. development of a(h7n9) candidate vaccine viruses (cvv) for pandemic preparedness purposes was initiated without delay. candidate vaccine viruses were derived by reverse genetics using the internal genes of a/puerto/rico/8/34 (pr8). the resulting a(h7n9) cvvs needed improvement because they had titers and antigen yields that were suboptimal for vaccine manufacturing in eggs, ...	2015	25962412
mammalian adaptation of influenza a(h7n9) virus is limited by a narrow genetic bottleneck.	human infection with avian influenza a(h7n9) virus is associated mainly with the exposure to infected poultry. the factors that allow interspecies transmission but limit human-to-human transmission are unknown. here we show that a/anhui/1/2013(h7n9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. in contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form. airborn ...	2015	25850788
evaluation of mdck cell-derived influenza h7n9 vaccine candidates in ferrets.	avian-origin influenza a (h7n9) viruses emerged as human pathogens in china in early 2013 and have killed >100 persons. influenza vaccines are mainly manufactured using egg-based technology which could not meet the surging demand during influenza pandemics. in this study, we evaluated cell-based influenza h7n9 vaccines in ferrets. an egg-derived influenza h7n9 reassortant vaccine virus was adapted in mdck cells. influenza h7n9 whole virus vaccine antigen was manufactured using a microcarrier-bas ...	2015	25799397
recombinant virus-like particles elicit protective immunity against avian influenza a(h7n9) virus infection in ferrets.	in march 2013, diagnosis of the first reported case of human infection with a novel avian-origin influenza a(h7n9) virus occurred in eastern china. most human cases have resulted in severe respiratory illness and, in some instances, death. currently there are no licensed vaccines against h7n9 virus, which continues to cause sporadic human infections. recombinant virus-like particles (vlps) have been previously shown to be safe and effective vaccines for influenza. in this study, we evaluated the ...	2015	25772674
neuraminidase mutations conferring resistance to oseltamivir in influenza a(h7n9) viruses.	human infections by avian influenza a(h7n9) virus entail substantial morbidity and mortality. treatment of infected patients with the neuraminidase (na) inhibitor oseltamivir was associated with emergence of viruses carrying na substitutions. in the na inhibition (ni) assay, r292k conferred highly reduced inhibition by oseltamivir, while e119v and i222k each caused reduced inhibition. to facilitate establishment of laboratory correlates of clinically relevant resistance, experiments were conduct ...	2015	25740997
impact of adjuvants on the immunogenicity and efficacy of split-virion h7n9 vaccine in ferrets.	an effective vaccine is urgently needed against the h7n9 avian influenza virus. we evaluated the immunogenicity and protective efficacy of a split-virion h7n9 vaccine with or without the oil-in-water adjuvants in ferrets.	2015	25712975
h7n9: preparing for the unexpected in influenza.	in the years prior to 2013, avian influenza a h7 viruses were a cause of significant poultry mortality; however, human illness was generally mild. in march 2013, a novel influenza a(h7n9) virus emerged in china as an unexpected cause of severe human illness with 36% mortality. chinese and other public health officials responded quickly, characterizing the virus and identifying more than 400 cases through use of new technologies and surveillance tools made possible by past preparedness and respon ...	2015	25386931
low virulence and lack of airborne transmission of the dutch highly pathogenic avian influenza virus h5n8 in ferrets.	highly pathogenic avian influenza (hpai) h5n8 viruses that emerged in poultry in east asia spread to europe and north america by late 2014. here we show that the european hpai h5n8 viruses differ from the korean and japanese hpai h5n8 viruses by several amino acids and that a dutch hpai h5n8 virus had low virulence and was not transmitted via the airborne route in ferrets. the virus did not cross-react with sera raised against pre-pandemic h5 vaccine strains. this data is useful for public healt ...	2015	26090682
pathogenesis of novel reassortant avian influenza virus a (h5n8) isolates in the ferret.	outbreaks of avian influenza virus h5n8 first occurred in 2014, and spread to poultry farms in korea. although there was no report of human infection by this subtype, it has the potential to threaten human public health. therefore, we evaluated the pathogenesis of h5n8 viruses in ferrets. two representative korean h5n8 strains did not induce mortality and significant respiratory signs after an intranasal challenge in ferrets. however, ferrets intratracheally infected with a/broiler duck/korea/bu ...	2015	25776760
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 ...	2015	26586437
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 ...	2015	26402787
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 ...	2015	26301691
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 ...	2015	26244768
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 ...	2015	26243288
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 ...	2015	26147369
identification of stabilizing mutations in an h5 hemagglutinin influenza virus protein.	highly pathogenic avian influenza viruses of the h5n1 subtype continue to circulate in poultry in asia, africa, and the middle east. recently, outbreaks of novel reassortant h5 viruses have also occurred in north america. although the number of human infections with highly pathogenic h5n1 influenza viruses continues to rise, these viruses remain unable to efficiently transmit between humans. however, we and others have identified h5 viruses capable of respiratory droplet transmission in ferrets. ...	2015	26719265
predicting disease severity and viral spread of h5n1 influenza virus in ferrets in the context of natural exposure routes.	although avian h5n1 influenza virus has yet to develop the capacity for human-to-human spread, the severity of the rare cases of human infection has warranted intensive follow-up of potentially exposed individuals that may require antiviral prophylaxis. for countries where antiviral drugs are limited, the world health organization (who) has developed a risk categorization for different levels of exposure to environmental, poultry, or human sources of infection. while these take into account the ...	2015	26656692
intranasal vaccination with a plant-derived h5 ha vaccine protects mice and ferrets against highly pathogenic avian influenza virus challenge.	highly pathogenic avian influenza h5n1 infection remains a public health threat and vaccination is the best measure of limiting the impact of a potential pandemic. mucosal vaccines have the advantage of eliciting immune responses at the site of viral entry, thereby preventing infection as well as further viral transmission. in this study, we assessed the protective efficacy of hemagglutinin (ha) from the a/indonesia/05/05 (h5n1) strain of influenza virus that was produced by transient expression ...	2015	25714901
pb2 segment promotes high-pathogenicity of h5n1 avian influenza viruses in mice.	h5n1 influenza viruses with high lethality are a continuing threat to humans and poultry. recently, h5n1 high-pathogenicity avian influenza virus (hpaiv) has been shown to transmit through aerosols between ferrets in lab experiments by acquiring some mutation. this is another deeply aggravated threat of h5n1 hpaiv to humans. to further explore the molecular determinant of h5n1 hpaiv virulence in a mammalian model, we compared the virulence of a/duck/guangdong/212/2004 (dk212) and a/quail/guangdo ...	2015	25713566
an anti-h5n1 influenza virus fcdart antibody is a highly efficacious therapeutic agent and prophylactic against h5n1 influenza virus infection.	highly pathogenic h5n1 avian influenza viruses are associated with severe disease in humans and continue to be a pandemic threat. while vaccines are available, other approaches are required for patients that typically respond poorly to vaccination, such as the elderly and the immunocompromised. to produce a therapeutic agent that is highly efficacious at low doses and is broadly specific against antigenically drifted h5n1 influenza viruses, we developed two neutralizing monoclonal antibodies and ...	2015	25673719
intranasal immunization of recombinant lactococcus lactis induces protection against h5n1 virus in ferrets.	the increasing outbreaks of highly pathogenic avian influenza a (hpai) h5n1 viruses in birds and human bring out an urgent need to develop a safe and effective vaccine to control and prevent h5n1 infection. lactococcus lactis (l. lactis) based vaccine platform is a promising approach for mucosal h5n1 vaccine development. intranasal immunization is the potential to induce mucosal immune response which is associated with protective immunity. to develop a safe and effective mucosal vaccine against ...	2015	25445345
adaptation of h9n2 aiv in guinea pigs enables efficient transmission by direct contact and inefficient transmission by respiratory droplets.	h9n2 avian influenza viruses circulate worldwide in poultry and have sporadically infected humans, raising concern whether h9n2 viruses have pandemic potential. here, we use a guinea pig model to examine whether serial passage results in adaptive viral changes that confer a transmissible phenotype to a wild-type h9n2 virus. after nine serial passages of an h9n2 virus through guinea pigs, productive transmission by direct contact occurred in 2/3 guinea pig pairs. the efficiency of transmission by ...	2015	26552719
characterization of an h9n2 avian influenza virus from a fringilla montifringilla brambling in northern china.	avian h9n2 influenza viruses circulating in domestic poultry populations are occasionally transmitted to humans. we report the genomic characterization of an h9n2 avian influenza virus (a/brambling/beijing/16/2012) first isolated from a healthy fringilla montifringilla brambling in northern china in 2012. phylogenetic analyses revealed that this h9n2 virus belongs to the bj/94-like sublineage. this virus had a low pathogenicity for chickens and was able to replicate at a low level in mouse lung ...	2015	25569456
replication capacity of avian influenza a(h9n2) virus in pet birds and mammals, bangladesh.	avian influenza a(h9n2) is an agricultural and public health threat. we characterized an h9n2 virus from a pet market in bangladesh and demonstrated replication in samples from pet birds, swine tissues, human airway and ocular cells, and ferrets. results implicated pet birds in the potential dissemination and zoonotic transmission of this virus.	2015	26583371
cross-protection against h7n9 influenza strains using a live-attenuated h7n3 virus vaccine.	in 2013, avian h7n9 influenza viruses were detected infecting people in china resulting in high mortality. influenza h7 vaccines that provide cross-protection against these new viruses are needed until specific h7n9 vaccines are ready to market. in this study, an available h7n3 cold-adapted, temperature sensitive, live attenuated influenza vaccine (laiv) elicited protective immune responses in ferrets against h7n9 viruses. the h7n3 laiv administered alone (by intranasal or subcutaneous administr ...	2015	25448100
a single immunization with modified vaccinia virus ankara-based influenza virus h7 vaccine affords protection in the influenza a(h7n9) pneumonia ferret model.	since the first reports in early 2013, >440 human cases of infection with avian influenza a(h7n9) have been reported including 122 fatalities. after the isolation of the first a(h7n9) viruses, the nucleotide sequences became publically available. based on the coding sequence of the influenza virus a/shanghai/2/2013 hemagglutinin gene, a codon-optimized gene was synthesized and cloned into a recombinant modified vaccinia virus ankara (mva). this mva-h7-sh2 viral vector was used to immunize ferret ...	2015	25246535
characterization of drug-resistant influenza a(h7n9) variants isolated from an oseltamivir-treated patient in taiwan.	patients contracting influenza a(h7n9) infection often developed severe disease causing respiratory failure. neuraminidase (na) inhibitors (nais) are the primary option for treatment, but information on drug-resistance markers for influenza a(h7n9) is limited.	2015	25124927
characterization of self-assembled virus-like particles of dromedary camel hepatitis e virus generated by recombinant baculoviruses.	dromedary camel hepatitis e virus (dchev), a novel hepatitis e virus, has been identified in dromedary camels in dubai, united arab emirates. the antigenicity, pathogenicity and epidemiology of this virus have been unclear. here we first used a recombinant baculovirus expression system to express the 13 and 111 n-terminus amino-acid-truncated dchev orf2 protein in insect tn5 cells, and we obtained two types of virus-like particles (vlps) with densities of 1.300 g/cm(3) and 1.285 g/cm(3), respect ...	2015	26160190
generation of hepatitis e virus-like particles of two new genotypes g5 and g6 and comparison of antigenic properties with those of known genotypes.	in addition to the four major genotypes (g1 through g4) known for human hepatitis e virus (hev), two new genotypes (g5 and g6) were suggested, based on unique viral nucleotide sequences derived from wild boars in japan. it has been unknown whether the virus of these new genotypes can cause hepatitis in humans; neither g5 nor g6 hev has been found in patients to date. to study the antigenic properties of g5 and g6 hev, we expressed n-terminus-truncated hev orf2 protein by a recombinant baculoviru ...	2015	25934534
monkeys and rats are not susceptible to ferret hepatitis e virus infection.	ferret hepatitis e virus (hev), a novel hepatitis e-like virus, has been identified in ferrets in the netherlands, japan, and the us. to determine whether ferret hev transmits to other animals, we inoculated laboratory rats (wistar), nude rats (long-evans-rnu/rnu), and cynomolgus monkeys with ferret hev (f4351) by intravenous injection. none of the animals demonstrated a positive sign for virus replication, indicating that rats and monkeys are not susceptible to ferret hev.	2015	25925280
characterization of two novel linear b-cell epitopes in the capsid protein of avian hepatitis e virus (hev) that are common to avian, swine, and human hevs.	antisera raised against the avian hepatitis e virus (hev) capsid protein are cross-reactive with human and swine hev capsid proteins. in this study, two monoclonal antibodies (mabs) against the avian hev capsid protein, namely, 3e8 and 1b5, were shown to cross-react with the swine hev capsid protein. the motifs involved in binding both mabs were identified and characterized using phage display biopanning, peptide synthesis, and truncated or mutated protein expression, along with indirect enzyme- ...	2015	25741007
ferret hepatitis e virus infection in japan.	we examined 85 fecal samples from pet ferrets in 10 animal hospitals in japan for the detection of ferret hepatitis e virus (hev) rna. we found that 6 (7.1%) of the samples were positive for ferret hev rna. phylogenetic analysis based on the partial orf1 indicated that these ferret hev strains were clearly separated from the netherlands strains and were divided into 2 distinct clusters. these results suggest that ferret hev is genetically diverse, and since ferrets are not indigenous to japan, f ...	2015	25420653
modeling human influenza infection in the laboratory.	influenza is the leading cause of death from an infectious cause. because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza a virus replication, the immune response to the virus, and the efficacy of novel therapies. this review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models - mice and ferrets - most frequently u ...	2015	26357484
synthetic long peptide influenza vaccine containing conserved t and b cell epitopes reduces viral load in lungs of mice and ferrets.	currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are required. in case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. we set out to develop a vaccine that provides protection against a broad range of influenza viruses. therefore, highly conserved parts of the influenza a virus (iav) were s ...	2015	26046664
generation of a transgenic mouse model of middle east respiratory syndrome coronavirus infection and disease.	the emergence of middle east respiratory syndrome-coronavirus (mers-cov) in the middle east since 2012 has caused more than 900 human infections with ∼40% mortality to date. animal models are needed for studying pathogenesis and for development of preventive and therapeutic agents against mers-cov infection. nonhuman primates (rhesus macaques and marmosets) are expensive models of limited availability. although a mouse lung infection model has been described using adenovirus vectors expressing h ...	2015	25589660
mouse adaptation of influenza b virus increases replication in the upper respiratory tract and results in droplet transmissibility in ferrets.	to investigate the molecular changes that allow influenza b viruses to adapt to new mammalian hosts, influenza b/florida/04/2006 was serially passaged in balb/c mice until highly virulent. the viral factors underlying this transition were then investigated in mice and ferrets. five viruses, including the wild-type virus (p0), three intermediate viruses (p5, p9, and p12), and a lethal mouse-adapted virus (p17 (ma)), harbored one to five amino acid substitutions in the hemagglutinin, m, np, and pa ...	2015	26526113
ferret airway epithelial cell cultures support efficient replication of influenza b virus but not mumps virus.	ferrets have become the model animal of choice for influenza pathology and transmission experiments as they are permissive and susceptible to human influenza a viruses. however, inoculation of ferrets with mumps virus (muv) did not lead to successful infections. we evaluated the use of highly differentiated ferret tracheal epithelium cell cultures, fte, for predicting the potential of ferrets to support respiratory viral infections. fte cultures supported productive replication of human influenz ...	2015	25953915
the immunomodulating v and w proteins of nipah virus determine disease course.	the viral determinants that contribute to nipah virus (niv)-mediated disease are poorly understood compared with other paramyxoviruses. here we use recombinant nivs (rnivs) to examine the contributions of the niv v and w proteins to niv pathogenesis in a ferret model. we show that a v-deficient rniv is susceptible to the innate immune response in vitro and behaves as a replicating non-lethal virus in vivo. remarkably, rniv lacking w expression results in a delayed and altered disease course with ...	2015	26105519
origin, evolution, and virulence of porcine deltacoronaviruses in the united states.	a novel porcine deltacoronavirus (pdcv) was first discovered in ohio and indiana in february 2014, rapidly spread to other states in the united states and canada, and caused significant economic loss in the swine industry. the origin and virulence of this novel porcine coronavirus are not known. here, we characterized u.s. pdcv isolates and determined their virulence in gnotobiotic and conventional piglets. genome analyses revealed that u.s. pdcv isolates possess unique genetic characteristics a ...	2015	25759498
multidrug-resistant proteus mirabilis isolated from newly weaned infant rhesus monkeys and ferrets.	proteus mirabilis is an important uropathogen that causes complicated urinary tract infection (uti) and induces diarrhea in infants.	2015	26301055
rabies virus infection in ferret badgers (melogale moschata subaurantiaca) in taiwan: a retrospective study.	fifteen ferret badgers (melogale moschata subaurantiaca), collected 2010-13 and stored frozen, were submitted for rabies diagnosis by direct fluorescent antibody test and reverse transcription pcr. we detected seven positive animal samples, including some from 2010, which indicated that the ferret badger population in taiwan had been affected by rabies prior to 2010.	2015	26267459
pyogranulomatous panniculitis in ferrets (mustela putorius furo) with intralesional demonstration of pseudomonas luteola.	one ferret (mustela putorius furo) from finland and two ferrets from austria, aged 1-4.5 years and of both genders, were presented with pyogranulomatous subcutaneous inflammation affecting the inguinal, preputial and femoral regions, respectively. histologically, microorganisms were detected within the lesions. the organisms had a capsule that stained positively by the periodic acid-schiff reaction. pseudomonas spp. were cultured from the lesions in two cases. in the third case, electron microsc ...	2015	25728813
replication and transmission of the novel bovine influenza d virus in a guinea pig model.	influenza d virus (fludv) is a novel influenza virus that infects cattle and swine. the goal of this study was to investigate the replication and transmission of bovine fludv in guinea pigs. following direct intranasal inoculation of animals, the virus was detected in nasal washes of infected animals during the first 7 days postinfection. high viral titers were obtained from nasal turbinates and lung tissues of directly inoculated animals. further, bovine fludv was able to transmit from the infe ...	2015	26378161
susceptibility of domestic animals to a pseudotype virus bearing rd-114 virus envelope protein.	retroviral vectors are used for gene transduction into cells and have been applied to gene therapy. retroviral vectors using envelope protein (env) of rd-114 virus, a feline endogenous retrovirus, have been used for gene transduction. in this study, we investigated the susceptibility to rd-114 env-pseudotyped virus in twelve domestic animals including cattle, sheep, horse, pig, dog, cat, ferret, mink, rabbit, rat, mouse, and quail. comparison of nucleotide sequences of asct2 (slc1a5), a receptor ...	2015	25936996
uridine diphosphate-glucuronosyltransferase (ugt) xenobiotic metabolizing activity and genetic evolution in pinniped species.	there are various interspecies differences in xenobiotic-metabolizing enzymes. it is known that cats show slow glucuronidation of drugs such as acetaminophen and strong side effects due to the ugt1a6 pseudogene. recently, the ugt1a6 pseudogene was found in the northern elephant seal and otariidae was suggested to be ugt1a6-deficient. from the results of measurements of uridine diphosphate-glucuronosyltransferase (ugt) activity using liver microsomes, the steller sea lion, northern fur seal, and ...	2015	26179383
transmission of h7n9 influenza viruses with a polymorphism at pb2 residue 627 in chickens and ferrets.	poultry exposure is a major risk factor for human h7n9 zoonotic infections, for which the mode of transmission remains unclear. we studied the transmission of genetically related poultry and human h7n9 influenza viruses differing by four amino acids, including the host determinant pb2 residue 627. a/silkie chicken/hk/1772/2014 (sck1772) and a/hk/3263/14 (hk3263) replicated to comparable titers in chickens, with superior oropharyngeal over cloacal shedding; both viruses transmitted efficiently am ...	2015	26202239
behavioral responses of predator-naïve dwarf hamsters (phodopus campbelli) to odor cues of the european ferret fed with different prey species.	many mammalian predators are able to identify their prey by odors and, vice versa, numerous prey species recognize predator odors as well. the present paper reports on the behavioral responses of predator-naïve dwarf hamsters (phodopus campbelli) towards the urine odors of carnivorous ferrets, which were raised on either a chicken, mouse or hamster diet. chemical composition from ferret urines of the different diet groups was analyzed, while quantitative differences in urinary volatile constitue ...	2015	26066723
ferret: a sentence-based literature scanning system.	the rapid pace of bioscience research makes it very challenging to track relevant articles in one's area of interest. medline, a primary source for biomedical literature, offers access to more than 20 million citations with three-quarters of a million new ones added each year. thus it is not surprising to see active research in building new document retrieval and sentence retrieval systems. we present ferret, a prototype retrieval system, designed to retrieve and rank sentences (and their docume ...	2015	26091670
animal models of middle east respiratory syndrome coronavirus infection.	the emergence of the middle east respiratory syndrome coronavirus (mers-cov) in 2012 marked the second time that a new, highly pathogenic coronavirus has emerged in the human population in the 21st century. in this review, we discuss the current state of knowledge of animal models of mers-cov infection. commonly used laboratory animal species such as syrian hamsters, mice and ferrets are not susceptible to mers-cov, due to differences in the mers-cov receptor dipeptidyl peptidase 4 (dpp4). the i ...	2015	26192750
fine-tuning of neurogenesis is essential for the evolutionary expansion of the cerebral cortex.	we used several animal models to study global and regional cortical surface expansion: the lissencephalic mouse, gyrencephalic normal ferrets, in which the parietal cortex expands more than the temporal cortex, and moderately lissencephalic ferrets, showing a similar degree of temporal and parietal expansion. we found that overall cortical surface expansion is achieved when specific events occur prior to surpragranular layer formation. (1) the subventricular zone (svz) shows substantial growth, ...	2015	23968831
anesthesia-related changes in information transfer may be caused by reduction in local information generation.	in anesthesia research it is an open question how general anesthetics lead to loss of consciousness (loc). it has been proposed that loc may be caused by the disruption of cortical information processing, preventing information integration. therefore, recent studies investigating information processing under anesthesia focused on changes in information transfer, measured by transfer entropy (te). however, often this complex technique was not applied rigorously, using time series in symbolic repr ...	2015	26737182
sequence and phylogenetic analysis identifies a putative novel gyrovirus 3 genotype in ferret feces.	the genomic sequence of a novel gyrovirus (gyv) 3 strain was detected from the fecal sample of a pet ferret. the length (2,359 nt) and the basic genomic structure of this strain was very similar to that of the single known gyv3 reference strain, whereas the genome sequence identity between the two strains was only 76 %. similarly, moderate sequence homology was found within the predicted protein coding regions, vp1 (nt, 72 %; aa, 76 %), vp2 (nt, 84 %; aa, 85 %), and vp3 (nt, 85 %; aa, 73 %). seq ...	2015	25319533
defective innate immunity and hyperinflammation in newborn cystic fibrosis transmembrane conductance regulator-knockout ferret lungs.	mucociliary clearance (mcc) and submucosal glands are major components of airway innate immunity that have impaired function in cystic fibrosis (cf). although both of these defense systems develop postnatally in the ferret, the lungs of newborn ferrets remain sterile in the presence of a functioning cystic fibrosis transmembrane conductance regulator gene. we evaluated several components of airway innate immunity and inflammation in the early cf ferret lung. at birth, the rates of mcc did not di ...	2015	25317669
mixed germ cell-sex cord-stromal tumor with a concurrent interstitial cell tumor in a ferret.	a 5-year-old male ferret presented with an enlarged canalicular testis in the left inguinal region. microscopically, the enlarged testis consisted of a diffuse intimately admixed proliferation of c-kit-positive germ cell-like and wilms tumor-1 protein-positive sertoli cell-like components, but no call-exner body was detected. in addition, the compact proliferation of steroidogenic acute regulatory protein-intense positive interstitial cells was identified in a separate peripheral area of the mas ...	2015	25311985
novel markers of gonadectomy-induced adrenocortical neoplasia in the mouse and ferret.	gonadectomy (gdx) induces sex steroid-producing adrenocortical tumors in certain mouse strains and in the domestic ferret. transcriptome analysis and dna methylation mapping were used to identify novel genetic and epigenetic markers of gdx-induced adrenocortical neoplasia in female dba/2j mice. markers were validated using a combination of laser capture microdissection, quantitative rt-pcr, in situ hybridization, and immunohistochemistry. microarray expression profiling of whole adrenal mrna fro ...	2015	25289806
survey of zoonotic dermatoses in client-owned exotic pet mammals in southern italy.	several 'exotic' mammalian species (e.g. rabbits, rodents, ferrets and hedgehogs) live in close proximity to humans as companion pets. skin diseases (sd) are frequent causes of morbidity in exotic pet mammals, and most of those sds have a zoonotic potential. the purpose of this study was to determine the frequencies and types of zoonotic dermatosis (zd) in client-owned, exotic pet mammals in southern italy. six-hundred and fifty-five medical records of exotic pet mammals examined between 2011 an ...	2015	24506806
comparison of a ferret model with an inanimate simulator for training novices in techniques for intubating neonates.	simulators for neonatal intubation training have improved, prompting us to compare a state-of-the-art simulator with live ferrets for training novice family-medicine residents in this crucial skill. after a scripted didactic presentation, we used a crossover study design and randomly assigned residents to receive simulator or live ferret training, after which they repeated the procedure by using the opposite method. participants were asked to report their level of confidence and competence befor ...	2015	26045454
animal models of adrenocortical tumorigenesis.	this comparative review highlights animal models of adrenocortical neoplasia useful either for mechanistic studies or translational research. three model species-mouse, ferret, and dog-are detailed. the relevance of each of these models to spontaneous and inherited adrenocortical tumors in humans is discussed.	2015	26038202
sexual dimorphism of sulcal morphology of the ferret cerebrum revealed by mri-based sulcal surface morphometry.	the present study quantitatively assessed sexual dimorphism of cortical convolution and sulcal morphology in young adult ferrets by mri-based sulcal surface morphometry. ex vivo t1-weighted (short tr/te) mri of the ferret cerebrum was acquired with high spatial resolution at 7-tesla. the degree of cortical convolution, evaluated quantitatively based on 3d mri data by sulcation index (si), was significantly greater in males (0.553 ± 0.036) than in females (0.502 ± 0.043) (p < 0.001). the rostroca ...	2015	25999821
the role of spectral cues in timbre discrimination by ferrets and humans.	timbre distinguishes sounds of equal loudness, pitch, and duration; however, little is known about the neural mechanisms underlying timbre perception. such understanding requires animal models such as the ferret in which neuronal and behavioral observation can be combined. the current study asked what spectral cues ferrets use to discriminate between synthetic vowels. ferrets were trained to discriminate vowels differing in the position of the first (f1) and second formants (f2), inter-formant d ...	2015	25994714
discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly.	gyrencephalic species develop folds in the cerebral cortex in a stereotypic manner, but the genetic mechanisms underlying this patterning process are unknown. we present a large-scale transcriptomic analysis of individual germinal layers in the developing cortex of the gyrencephalic ferret, comparing between regions prospective of fold and fissure. we find unique transcriptional signatures in each germinal compartment, where thousands of genes are differentially expressed between regions, includ ...	2015	25916825
ferret wellness management and environmental enrichment.	the domestic ferret is a commonly kept companion animal. knowledge of proper husbandry of companion ferrets and their common disease processes by veterinarians assists pet owners in providing the healthiest environment possible. attentiveness to the environmental needs of pet ferrets results in physically and psychologically healthy animals and a positive, enriched relationship with owners.	2015	25902271
retrocaval ureter in a ferret.		2015	25819617
ferret models of viral pathogenesis.	emerging and well-known viral diseases remain one the most important global public health threats. a better understanding of their pathogenesis and mechanisms of transmission requires animal models that accurately reproduce these aspects of the disease. here we review the role of ferrets as an animal model for the pathogenesis of different respiratory viruses with an emphasis on influenza and paramyxoviruses. we will describe the anatomic and physiologic characteristics that contribute to the na ...	2015	25816764
coevolution of radial glial cells and the cerebral cortex.	radial glia cells play fundamental roles in the development of the cerebral cortex, acting both as the primary stem and progenitor cells, as well as the guides for neuronal migration and lamination. these critical functions of radial glia cells in cortical development have been discovered mostly during the last 15 years and, more recently, seminal studies have demonstrated the existence of a remarkable diversity of additional cortical progenitor cell types, including a variety of basal radial gl ...	2015	25808466
epibatidine blocks eye-specific segregation in ferret dorsal lateral geniculate nucleus during stage iii retinal waves.	the segregation and maintenance of eye-specific inputs in the dorsal lateral geniculate nucleus (dlgn) during early postnatal development requires the patterned spontaneous activity of retinal waves. in contrast to the development of the mouse, ferret eye-specific segregation is not complete at the start of stage iii glutamatergic retinal waves, and the remaining overlap is limited to the c/c1 lamina of the dlgn. to investigate the role of patterned spontaneous activity in this late segregation, ...	2015	25794280
optimization of recombinant adeno-associated virus-mediated expression for large transgenes, using a synthetic promoter and tandem array enhancers.	the packaging capacity of recombinant adeno-associated viral (raav) vectors limits the size of the promoter that can be used to express the 4.43-kb cystic fibrosis transmembrane conductance regulator (cftr) cdna. to circumvent this limitation, we screened a set of 100-mer synthetic enhancer elements, composed of ten 10-bp repeats, for their ability to augment cftr transgene expression from a short 83-bp synthetic promoter in the context of an raav vector designed for use in the cystic fibrosis ( ...	2015	25763813
single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex.	the human cerebral cortex depends for its normal development and size on a precisely controlled balance between self-renewal and differentiation of diverse neural progenitor cells. specialized progenitors that are common in humans but virtually absent in rodents, called outer radial glia (org), have been suggested to be crucial to the evolutionary expansion of the human cortex. we combined progenitor subtype-specific sorting with transcriptome-wide rna sequencing to identify genes enriched in hu ...	2015	25734491
single-unit analysis of somatosensory processing in the core auditory cortex of hearing ferrets.	the recent findings in several species that the primary auditory cortex processes non-auditory information have largely overlooked the possibility of somatosensory effects. therefore, the present investigation examined the core auditory cortices (anterior auditory field and primary auditory cortex) for tactile responsivity. multiple single-unit recordings from anesthetised ferret cortex yielded histologically verified neurons (n = 311) tested with electronically controlled auditory, visual and t ...	2015	25728185
ferret and pig models of cystic fibrosis: prospects and promise for gene therapy.	large animal models of genetic diseases are rapidly becoming integral to biomedical research as technologies to manipulate the mammalian genome improve. the creation of cystic fibrosis (cf) ferrets and pigs is an example of such progress in animal modeling, with the disease phenotypes in the ferret and pig models more reflective of human cf disease than mouse models. the ferret and pig cf models also provide unique opportunities to develop and assess the effectiveness of gene and cell therapies ...	2015	25675143
your kid could not have done that: even untutored observers can discern intentionality and structure in abstract expressionist art.	can people with no special knowledge about art detect the skill, intentionality, and expressed meanings in non-representational art? hawley-dolan and winner (2011) showed participants without training in art images of abstract expressionist paintings paired with superficially similar works by children or animals and asked them which they preferred and which was a better work of art. participants selected the works by artists in response to both questions at a rate above chance. in study 1, we us ...	2015	25659538
histochemical and immunohistochemical characterization of chordoma in ferrets.	chordomas of the tip of the tail in 6 ferrets were examined using histopathological, histochemical and immunohistochemical procedures. histopathologically, round neoplastic cells containing numerous cytoplasmic vacuoles of varying sizes, categorized as "physaliphorous cells", were observed in the amorphous eosinophilic or pale basophilic myxoid stroma. physaliphorous cells were arranged in lobules and in a "chordoid" or "cobblestone" manner. the neoplasms were diagnosed as benign chordoma withou ...	2015	25648567
auditory and visual interactions between the superior and inferior colliculi in the ferret.	the integration of visual and auditory spatial information is important for building an accurate perception of the external world, but the fundamental mechanisms governing such audiovisual interaction have only partially been resolved. the earliest interface between auditory and visual processing pathways is in the midbrain, where the superior (sc) and inferior colliculi (ic) are reciprocally connected in an audiovisual loop. here, we investigate the mechanisms of audiovisual interaction in the ...	2015	25645363
evaluation of a ferret-specific formula for determining body surface area to improve chemotherapeutic dosing.	to use ct-derived measurements to create a ferret-specific formula for body surface area (bsa) to improve chemotherapeutic dosing.	2015	25629911
studies on influenza virus transmission between ferrets: the public health risks revisited.		2015	25616377
reply to "studies on influenza virus transmission between ferrets: the public health risks revisited".		2015	25616376
the development of cortical circuits for motion discrimination.	stimulus discrimination depends on the selectivity and variability of neural responses, as well as the size and correlation structure of the responsive population. for direction discrimination in visual cortex, only the selectivity of neurons has been well characterized across development. here we show in ferrets that at eye opening, the cortical response to visual stimulation exhibits several immaturities, including a high density of active neurons that display prominent wave-like activity, a h ...	2015	25599224
loss of cftr function leads to pancreatic destruction in larval zebrafish.	the development and function of many internal organs requires precisely regulated fluid secretion. a key regulator of vertebrate fluid secretion is an anion channel, the cystic fibrosis transmembrane conductance regulator (cftr). loss of cftr function leads to defects in fluid transport and cystic fibrosis (cf), a complex disease characterized by a loss of fluid secretion and mucus buildup in many organs including the lungs, liver, and pancreas. several animal models including mouse, ferret and ...	2015	25592226
complementary adaptive processes contribute to the developmental plasticity of spatial hearing.	spatial hearing evolved independently in mammals and birds and is thought to adapt to altered developmental input in different ways. we found, however, that ferrets possess multiple forms of plasticity that are expressed according to which spatial cues are available, suggesting that the basis for adaptation may be similar across species. our results also provide insight into the way sound source location is represented by populations of cortical neurons.	2015	25581359
chf6001 ii: a novel phosphodiesterase 4 inhibitor, suitable for topical pulmonary administration--in vivo preclinical pharmacology profile defines a potent anti-inflammatory compound with a wide therapeutic window.	chf6001 [(s)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide] is a novel phosphodiesterase 4 (pde4) inhibitor designed for use in pulmonary diseases by inhaled administration. intratracheal administration of chf6001 to ovalbumin-sensitized brown-norway rats suppressed the antigen-induced decline of lung functions (ed50 = 0.1 µmol/kg) and antigen-induced eosinophilia (ed50 = 0.03 µmol/kg) when ad ...	2015	25576073
rhythmic 3-4hz discharge is insufficient to produce cortical bold fmri decreases in generalized seizures.	absence seizures are transient episodes of impaired consciousness accompanied by 3-4 hz spike-wave discharge on electroencephalography (eeg). human functional magnetic resonance imaging (fmri) studies have demonstrated widespread cortical decreases in the blood oxygen-level dependent (bold) signal that may play an important role in the pathophysiology of these seizures. animal models could provide an opportunity to investigate the fundamental mechanisms of these changes, however they have so far ...	2015	25562830
isolation, characterization, and functional analysis of ferret lymphatic endothelial cells.	the lymphatic endothelium (le) serves as a conduit for transport of immune cells and soluble antigens from peripheral tissues to draining lymph nodes (lns), contributing to development of host immune responses and possibly dissemination of microbes. lymphatic endothelial cells (lecs) are major constituents of the lymphatic endothelium. these specialized cells could play important roles in initiation of host innate immune responses through sensing of pathogen-associated molecular patterns (pamps) ...	2015	25540877
frequency-band signatures of visual responses to naturalistic input in ferret primary visual cortex during free viewing.	neuronal firing responses in visual cortex reflect the statistics of visual input and emerge from the interaction with endogenous network dynamics. artificial visual stimuli presented to animals in which the network dynamics were constrained by anesthetic agents or trained behavioral tasks have provided fundamental understanding of how individual neurons in primary visual cortex respond to input. in contrast, very little is known about the mesoscale network dynamics and their relationship to mic ...	2015	25498982
toying with fate: redirecting the differentiation of adrenocortical progenitor cells into gonadal-like tissue.	cell fate decisions are integral to zonation and remodeling of the adrenal cortex. animal models exhibiting ectopic differentiation of gonadal-like cells in the adrenal cortex can shed light on the molecular mechanisms regulating steroidogenic cell fate. in one such model, prepubertal gonadectomy (gdx) of mice triggers the formation of adrenocortical neoplasms that resemble luteinized ovarian stroma. transcriptomic analysis and genome-wide dna methylation mapping have identified genetic and epig ...	2015	25498963
repeated threat (without harm) in a living environment potentiates defensive behavior.	children exposed to neighborhood violence have higher rates of aggression, but it is unclear whether aggression is associated with threat, harm or the combination of factors. all animals, including humans, experience threat as they leave the safety of home and risk harm to gather resources (foraging). to better understand how selective environmental variables drive behavioral tendencies, we developed a semi-naturalistic living environment that includes the need to navigate across space to obtain ...	2015	25446759
congenital abnormalities of the vertebral column in ferrets.	vertebral column pathologies requiring surgical intervention have been described in pet ferrets, however little information is available on the normal vertebral formula and congenital variants in this species. the purpose of this retrospective study was to describe vertebral formulas and prevalence of congenital vertebral anomalies in a sample of pet ferrets. radiographs of 172 pet ferrets (96 males and 76 females) were included in this retrospective study. in 143 ferrets (83.14%), five differen ...	2015	25124147
mapping influenza transmission in the ferret model to transmission in humans.	the controversy surrounding 'gain-of-function' experiments on high-consequence avian influenza viruses has highlighted the role of ferret transmission experiments in studying the transmission potential of novel influenza strains. however, the mapping between influenza transmission in ferrets and in humans is unsubstantiated. we address this gap by compiling and analyzing 240 estimates of influenza transmission in ferrets and humans. we demonstrate that estimates of ferret secondary attack rate ( ...	2015	26329460
vaccine-elicited antibody that neutralizes h5n1 influenza and variants binds the receptor site and polymorphic sites.	antigenic drift of circulating seasonal influenza viruses necessitates an international vaccine effort to reduce the impact on human health. a critical feature of the seasonal vaccine is that it stimulates an already primed immune system to diversify memory b cells to recognize closely related, but antigenically distinct, influenza glycoproteins (hemagglutinins). influenza pandemics arise when hemagglutinins to which no preexisting adaptive immunity exists acquire the capacity to infect humans. ...	2015	26170302
is it the end of the nervous breakdown on avian influenza?		2015	26106976
asymptomatic middle east respiratory syndrome coronavirus infection in rabbits.	the ability of middle east respiratory syndrome coronavirus (mers-cov) to infect small animal species may be restricted given the fact that mice, ferrets, and hamsters were shown to resist mers-cov infection. we inoculated rabbits with mers-cov. although virus was detected in the lungs, neither significant histopathological changes nor clinical symptoms were observed. infectious virus, however, was excreted from the upper respiratory tract, indicating a potential route of mers-cov transmission i ...	2015	25810539
identification of hemagglutinin residues responsible for h3n2 antigenic drift during the 2014-2015 influenza season.	influenza vaccines must be updated regularly because influenza viruses continuously acquire mutations in antibody binding sites of hemagglutinin (ha). the majority of h3n2 strains circulating in the northern hemisphere during the 2014-2015 season are antigenically mismatched to the a/texas/50/2012 h3n2 vaccine strain. recent h3n2 strains possess several new ha mutations, and it is unknown which of these mutations contribute to the 2014-2015 vaccine mismatch. here, we use reverse genetics to demo ...	2015	26119736
ferretting out the facts behind the h5n1 controversy.	recent recommendations by the national science advisory board for biosecurity (nsabb) to redact key methodological details of two studies involving mammal-to-mammal transmission of the h5n1 (h5) subtype influenza viruses, has led to a temporary moratorium on all research involving live h5n1 or h5 ha reassortant viruses shown to be transmissible in ferrets. herein, i review the events which led to this impasse and comment on their impact.	2015	22402712
novel calicivirus from a ferret badger (melogale moschata) in china.	we describe the isolation and complete genome sequence of a new calicivirus, fbcv-jx12, isolated from a ferret badger (melogale moschata). comparison of fbcv-jx12 with other vesiviruses revealed that it shared the highest amino acid sequence identities of 71.6, 60.5, and 59.3% in the nonstructural protein, vp1, and vp2, respectively, with mcv-dl2007 (mink calicivirus). phylogenetic analysis of the whole genomic sequence showed that it clustered most closely with mcv-dl2007 of the genus vesivirus ...	2015	25976558