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influenza virus subtypes in aquatic birds of eastern germany.we report the findings of a 12-year surveillance study (1977-89) of avian influenza a viruses in eastern germany. viruses were isolated directly from feral ducks (n = 236) and other wild birds (n = 89); from domestic ducks (n = 735) living on a single farm; and from white pekin ducks (n = 193) used as sentinels for populations of wild aquatic birds; mainly sea birds. the efficiency of virus isolation was 9.9% overall, with considerable variability noted among species: 8.7% in wild ducks, 0.9% in ...19948198436
a dna transfection system for generation of influenza a virus from eight plasmids.we have developed an eight-plasmid dna transfection system for the rescue of infectious influenza a virus from cloned cdna. in this plasmid-based expression system, viral cdna is inserted between the rna polymerase i (pol i) promoter and terminator sequences. this entire pol i transcription unit is flanked by an rna polymerase ii (pol ii) promoter and a polyadenylation site. the orientation of the two transcription units allows the synthesis of negative-sense viral rna and positive-sense mrna fr ...200010801978
efficacy of zanamivir against avian influenza a viruses that possess genes encoding h5n1 internal proteins and are pathogenic in mammals.in 1997, an avian h5n1 influenza virus, a/hong kong/156/97 (a/hk/156/97), caused six deaths in hong kong, and in 1999, an avian h9n2 influenza virus infected two children in hong kong. these viruses and a third avian virus [a/teal/hk/w312/97 (h6n1)] have six highly related genes encoding internal proteins. additionally, a/chicken/hk/g9/97 (h9n2) virus has pb1 and pb2 genes that are highly related to those of a/hk/156/97 (h5n1), a/teal/hk/w312/97 (h6n1), and a/quail/hk/g1/97 (h9n2) viruses. becau ...200111257037
genetic characterization of h5n1 avian influenza viruses isolated in southern china during the 2003-04 avian influenza outbreaks.the recent h5n1 avian influenza outbreaks in asia spread over more than 8 countries. it has caused enormous economic loss and grand challenges for the public health. during these breakouts we isolated three strains of h5n1 avian influenza virus (aiv) from chickens and one from duck in different farms of southern china. we completely sequenced these four aivs. molecular characterization demonstrated that these strains retain the reported h5n1 aiv sequence properties relevant to virus virulence an ...200515717120
[phylogenetic analysis of the surface glycoprotein genes of an aquatic bird origin influenza virus isolate a/duck/yangzhou/233/2002 (h6n2)].several h6 subtype avian a influenza viruses were isolated from aquatic birds in some live bird markets when we surveyed the ecology of the influenza in east china for more than two years and identified by specific rt-pcr. in this paper, the hemagglutinin (ha) and neuraminidase (na) gene of one representative virus named a/duck/yangzhou/233/ 2002 (h6n2) (dk/yz/233/02) had been sequenced. phylogenetic analysis of the h6 gene sequences available in the influenza sequence database showed that the d ...200516245856
molecular epizootiology of recurrent low pathogenic avian influenza by h9n2 subtype virus in korea.the first outbreak of low pathogenic avian influenza (lpai), h9n2 virus subtype, in 1996 prompted an eradication response, but lpai returned to korea in 1999. the relationship between the first and the recurrent viruses is unclear. to determine the molecular epizootiology of recurrent lpai, we performed phylogenetic analysis with partial nucleotide sequences of four gene segments (ha, na, np and pb2) from eight chicken-origin h9n2 viruses. the recurrent h9n2 viruses showed higher nucleotide simi ...200616854644
sequence comparison between two quasi strains of h6n1 with different pathogenicity from a single parental isolate.relationships between gene change and virulence for hemagglutinin (ha) subtypes of avian influenza virus remain inconclusive. in this study, sequences of these nearly identical virus strains were obtained in order to elucidate the relationship between molecular determinants and virulence.200616926974
avian influenza virus screening in wild waterfowl in norway, 2005.the prevalence of influenza a virus infection, and the distribution of different subtypes of the virus, were studied in 604 geese and ducks shot during ordinary hunting 2005. the study was based upon molecular screening of cloacal swabs taken by the hunters. the sampling included the following species: greylag (anser anser), mallard (anas platyrhynchos), wigeon (anas penelope), teal (anas crecca), goosander (mergus merganser), tufted duck (aythya fuligula), common scoter (melanitta nigra), golde ...200717494599
cloning of the canine rna polymerase i promoter and establishment of reverse genetics for influenza a and b in mdck cells.recent incidents where highly pathogenic influenza a h5n1 viruses have spread from avian species into humans have prompted the development of cell-based production of influenza vaccines as an alternative to or replacement of current egg-based production. madin-darby canine kidney (mdck) cells are the primary cell-substrate candidate for influenza virus production but an efficient system for the direct rescue of influenza virus from cloned influenza cdnas in mdck cells did not exist. the objectiv ...200717956624
development of vaccine strains of h5 and h7 influenza viruses.to establish vaccine strains of h5 and h7 influenza viruses, a/duck/hokkaido/vac-1/04 (h5n1) [vac-1/04 (h5n1)], a/duck/hokkaido/vac-3/07 (h5n1) [vac-3/07 (h5n1)], and a/duck/hokkaido/ vac-2/04 (h7n7) [vac-2/04 (h7n7)] were generated from non-pathogenic avian influenza viruses isolated from migratory ducks. vac-1/04 (h5n1) and vac-3/07 (h5n1) were generated by genetic reassortment between h5n2 or h5n3 virus as an ha gene provider and h7n1 or h6n1 viruses as an na gene provider. vac-2/04 (h7n7) wa ...200818318111
origin of the 1918 spanish influenza virus: a comparative genomic analysis.to test the avian-origin hypothesis of the 1918 spanish influenza virus we surveyed influenza sequences from a broad taxonomic distribution and collected 65 full-length genomes representing avian, human and "classic" swine h1n1 lineages in addition to numerous other swine (h1n2, h3n1, and h3n2), human (h2n2, h3n2, and h5n1), and avian (h1n1, h4n6, h5n1, h6n1, h6n6, h6n8, h7n3, h8n4, h9n2, and h13n2) subtypes. amino acids from all eight segments were concatenated, aligned, and used for phylogenet ...200818353690
transmission of avian influenza virus (h3n2) to dogs.in south korea, where avian influenza virus subtypes h3n2, h5n1, h6n1, and h9n2 circulate or have been detected, 3 genetically similar canine influenza virus (h3n2) strains of avian origin (a/canine/korea/01/2007, a/canine/korea/02/2007, and a/canine/korea/03/2007) were isolated from dogs exhibiting severe respiratory disease. to determine whether the novel canine influenza virus of avian origin was transmitted among dogs, we experimentally infected beagles with this influenza virus (h3n2) isola ...200818439355
surveillance of avian influenza viruses in northern pintails (anas acuta) in tohoku district, japan.among winter migratory waterfowl, northern pintails (anas acuta), in one of the largest flocks in tohoku district, northeast japan, were surveyed for influenza a viruses at five wintering sites in three prefectures, viz., aomori, akita, and miyagi. a total of 38 influenza a viruses were isolated from 2066 fecal samples collected during november 2006 through march 2007. the overall isolation rate was 1.84%. eleven different subtypes were isolated, including nine h5n2, seven h6n8, seven h10n1, fou ...200818459295
gene segment reassortment between american and asian lineages of avian influenza virus from waterfowl in the beringia area.since prehistoric times, the bering strait area (beringia) has served as an avenue of dispersal between the old and the new worlds. on a field expedition to this area, we collected fecal samples from dabbling ducks, geese, shorebirds, and gulls on the chukchi peninsula, siberia, and pt. barrow, alaska, and characterized the subtypes of avian influenza virus present in them. four of 202 samples (2%) from alaska were positive for influenza a virus rna in two independent polymerase chain reaction ( ...200818637721
evaluation of live attenuated influenza a virus h6 vaccines in mice and ferrets.avian influenza a virus a/teal/hk/w312/97 (h6n1) possesses seven gene segments that are highly homologous to those of highly pathogenic human influenza h5n1 viruses, suggesting that a w312-like h6n1 virus might have been involved in the generation of the a/hk/97 h5n1 viruses. the continuous circulation and reassortment of influenza h6 subtype viruses in birds highlight the need to develop an h6 vaccine to prevent potential influenza pandemics caused by the h6 viruses. based on the serum antibody ...200918945773
genetic relatedness of h6 subtype avian influenza viruses isolated from wild birds and domestic ducks in korea and their pathogenicity in animals.we report the genetic characterization of h6 avian influenza (ai) viruses isolated from domestic ducks and wild birds in korea between april 2008 and april 2009. a phylogenetic analysis showed that the h6n1 viruses of wild birds and domestic ducks were of the same genotype (k-1) and were similar to the h6n1 virus isolated from a live poultry market in 2003, as six of the eight gene segments of those viruses had a common source. however, the h6n2 viruses of domestic poultry were separated into fo ...201019812266
surveillance of avian influenza virus in wild bird fecal samples from south korea, 2003-2008.we analyzed the results from nationwide surveillance of avian influenza (ai) from birds in south korea's major wild bird habitats and the demilitarized zone of south korea, 2003-2008. of 28,214 fecal samples analyzed, 225 yielded influenza viruses, for a prevalence of 0.8%. hemagglutinin (ha) subtypes h1-h12 and all nine neuraminidase (na) subtypes were detected. the dominant ha subtypes were h6, h1, and h4, and the most common na subtypes were n2, n1, and n6. among the 38 ha/na subtype combinat ...201020688693
an open label phase i trial of a live attenuated h6n1 influenza virus vaccine in healthy adults.we describe the results of an open label phase i trial of a live attenuated h6n1 influenza virus vaccine (clinicaltrials.gov identifier: nct00734175).201121377509
the infection of chicken tracheal epithelial cells with a h6n1 avian influenza virus.sialic acids (sas) linked to galactose (gal) in α2,3- and α2,6-configurations are the receptors for avian and human influenza viruses, respectively. we demonstrate that chicken tracheal ciliated cells express α2,3-linked sa, while goblet cells mainly express α2,6-linked sa. in addition, the plant lectin mal-ii, but not maa/mal-i, is bound to the surface of goblet cells, suggesting that sa2,3-linked oligosaccharides with galβ1-3galnac subterminal residues are specifically present on the goblet ce ...201121573102
different immune responses to three different vaccines following h6n1 low pathogenic avian influenza virus challenge in taiwanese local chicken breeds.h6n1 low pathogenic avian influenza virus (lpaiv) are frequently isolated in taiwan and lead to significant economic losses, either directly or indirectly through association with other infectious diseases. this study investigates immune responses to three different vaccines following a h6n1 challenge in different local breeds.201121645314
molecular evolution of the h6 subtype influenza a viruses from poultry in eastern china from 2002 to 2010.although extensive data demonstrates that the majority of h6 duck isolates belonged to a single h6n2 virus lineage with a single gene constellation in southern china from 2000 to 2005, the prevalence of h6n2 virus in poultry in eastern china is largely unknown.201121999472
influenza-a viruses in ducks in northwestern minnesota: fine scale spatial and temporal variation in prevalence and subtype diversity.waterfowl from northwestern minnesota were sampled by cloacal swabbing for avian influenza virus (aiv) from july-october in 2007 and 2008. aiv was detected in 222 (9.1%) of 2,441 ducks in 2007 and in 438 (17.9%) of 2,452 ducks in 2008. prevalence of aiv peaked in late summer. we detected 27 aiv subtypes during 2007 and 31 during 2008. ten hemagglutinin (ha) subtypes were detected each year (i.e., h1, 3-8, and 10-12 during 2007; h1-8, 10 and 11 during 2008). all neuraminidase (na) subtypes were d ...201121931636
development of an antigen-capture enzyme-linked immunosorbent assay using monoclonal antibodies for detecting h6 avian influenza viruses.the h6 subtype of avian influenza virus (aiv) infection occurs frequently in wild and domestic birds. aiv antigen detection is preferred for controlling aiv as birds are infected before they produce antibodies. the purpose of this study was to develop an early diagnostic method for aiv detection. six monoclonal antibodies (mabs) developed from a field h6n1 aiv strain were tested for their ability to bind to viruses. the two that showed the greatest binding ability to aivs were used for antigen d ...201122206824
Isolation and characterization of H6N1 and H9N2 avian influenza viruses from Ducks in Hanoi, Vietnam.We report the genetic characterization of low pathogenic avian influenza (LPAI) viruses isolated from domestic ducks in northern Vietnam in 2009. In total, 22 influenza A viruses consisting of 21 H6N1 subtypes and one H9N2 subtype were isolated from 1488 ducks collected in February, March, and April 2009, accounting the overall virus isolation rate for 1.5%. No H5N1 strain was isolated in this study. Phylogenetic analysis indicated that all the eight genes of the H6N1 and H9N2 subtypes analyzed ...201122108585
prospective of genomics in revealing transmission, reassortment and evolution of wildlife-borne avian influenza a (h5n1) viruses.the outbreak of highly pathogenic avian influenza (hpai) h5n1 disease has led to significant loss of poultry and wild life and case fatality rates in humans of 60%. wild birds are natural hosts for all avian influenza virus subtypes and over120 bird species have been reported with evidence of h5n1 infection. influenza a viruses possess a segmented rna genome and are characterized by frequently occurring genetic reassortment events, which play a very important role in virus evolution and the spre ...201122547954
characterization of a low pathogenic avian influenza virus (h6n1) isolated from turkeys.an avian influenza virus (aiv), a/turkey/israel/09 subtype h6n1, was isolated from turkey poults exhibiting typical pathology associated with aiv infection. the virus was characterized by rt-pcr using aiv subtype-specific primers and by the haemagglutination inhibition test using aiv subtype-specific antisera. the virus has an intravenous pathogenicity index of 0 and possessed a nucleotide sequence at the cleavage site of the hemagglutinin gene, pqietr*glf, associated with avian influenza viruse ...201123074655
avian influenza virus wild bird surveillance in the azov and black sea regions of ukraine (2010-2011).the azov and black sea basins are part of the transcontinental wild bird migration routes from northern asia and europe to the mediterranean, africa, and southwest asia. these regions constitute an area of transit, stops during migration, and nesting for many different bird species. from september 2010 to september 2011, a wild bird surveillance study was conducted in these regions to identify avian influenza viruses. biological samples consisting of cloacal and tracheal swabs and fecal samples ...201223402128
surveillance and characterization of avian influenza viruses from migratory water birds in eastern hokkaido, the northern part of japan, 2009-2010.avian influenza virus (aiv) surveillance was conducted around a small pond in obihiro, eastern hokkaido, japan. eleven aivs were isolated from a total of 1,269 fecal samples of migratory wild birds collected during 2009 and 2010. the sample number covered approximately 60 % of the total number of birds observed during sampling periods. the subtypes of the isolates included h3n8 (4 isolates), h5n2 (3), h6n2 (2), h6n1 (1), and h11n2 (1). the h3n8 subtype was most prevalent as in the previous studi ...201223264106
little evidence of avian or equine influenza virus infection among a cohort of mongolian adults with animal exposures, 2010-2011.avian (aiv) and equine influenza virus (eiv) have been repeatedly shown to circulate among mongolia's migrating birds or domestic horses. in 2009, 439 mongolian adults, many with occupational exposure to animals, were enrolled in a prospective cohort study of zoonotic influenza transmission. sera were drawn upon enrollment and again at 12 and 24 months. participants were contacted monthly for 24 months and queried regarding episodes of acute influenza-like illnesses (ili). cohort members confirm ...201424465622
avian influenza a viruses: evolution and zoonotic infection.although efficient human-to-human transmission of avian influenza virus has yet to be seen, in the past two decades avian-to-human transmission of influenza a viruses has been reported. influenza a/h5n1, in particular, has repeatedly caused human infections associated with high mortality, and since 1998 the virus has evolved into many clades of variants with significant antigenic diversity. in 2013, three (a/h7n9, a/h6n1, and a/h10n8) novel avian influenza viruses (aivs) breached the animal-huma ...201627486732
challenges and strategies of laboratory diagnosis for newly emerging influenza viruses in taiwan: a decade after sars.since the first case of severe acute respiratory syndrome (sars) in taiwan was identified in march 2003, viral respiratory infections, in particular the influenza virus, have become a national public health concern. taiwan would face a serious threat of public health problems if another sars epidemic overlapped with a flu outbreak. after sars, the taiwan centers for disease control accelerated and strengthened domestic research on influenza and expanded the exchange of information with internati ...201526290876
structure and receptor binding preferences of recombinant hemagglutinins from avian and human h6 and h10 influenza a virus subtypes.during 2013, three new avian influenza a virus subtypes, a(h7n9), a(h6n1), and a(h10n8), resulted in human infections. while the a(h7n9) virus resulted in a significant epidemic in china across 19 provinces and municipalities, both a(h6n1) and a(h10n8) viruses resulted in only a few human infections. this study focuses on the major surface glycoprotein hemagglutinins from both of these novel human viruses. the detailed structural and glycan microarray analyses presented here highlight the idea t ...201525673707
zoonotic infections with avian influenza a viruses and vaccine preparedness: a game of "mix and match".various direct avian-to-human transmissions of influenza a virus subtypes upon exposure to infected poultry have been previously observed in the past decades. although some of these strains caused lethal infections, the lack of sustained person-to-person transmission has been the major factor that prevented these viruses from causing new pandemics. in 2013, three (a/h7n9, a/h6n1, and a/h10n8) novel avian influenza viruses (aivs) yet again breached the animal-human host species barrier in asia. n ...201425003087
genetically diverse low pathogenicity avian influenza a virus subtypes co-circulate among poultry in bangladesh.influenza virus surveillance, poultry outbreak investigations and genomic sequencing were assessed to understand the ecology and evolution of low pathogenicity avian influenza (lpai) a viruses in bangladesh from 2007 to 2013. we analyzed 506 avian specimens collected from poultry in live bird markets and backyard flocks to identify influenza a viruses. virus isolation-positive specimens (n = 50) were subtyped and their coding-complete genomes were sequenced. the most frequently identified subtyp ...201627010791
little evidence of subclinical avian influenza virus infections among rural villagers in cambodia.in 2008, 800 adults living within rural kampong cham province, cambodia were enrolled in a prospective cohort study of zoonotic influenza transmission. after enrollment, participants were contacted weekly for 24 months to identify acute influenza-like illnesses (ili). follow-up sera were collected at 12 and 24 months. a transmission substudy was also conducted among the family contacts of cohort members reporting ili who were influenza a positive. samples were assessed using serological or molec ...201424819948
a prospective study of romanian agriculture workers for zoonotic influenza infections.in this prospective study we sought to examine seroepidemiological evidence for acute zoonotic influenza virus infection among romanian agricultural workers.201424869796
human monoclonal antibody 81.39a effectively neutralizes emerging influenza a viruses of group 1 and 2 hemagglutinins.the pandemic threat posed by emerging zoonotic influenza a viruses necessitates development of antiviral agents effective against various antigenic subtypes. human monoclonal antibody (hmab) targeting the hemagglutinin (ha) stalk offers a promising approach to control influenza virus infections. here, we investigated the ability of the hmab 81.39a to inhibit in vitro replication of human and zoonotic viruses, representing 16 ha subtypes. the majority of viruses were effectively neutralized by 81 ...201627630240
early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation.pigs are evidently more resistant to avian than swine influenza a viruses, mediated in part through frontline epithelial cells and alveolar macrophages (am). although porcine am (pam) are crucial in influenza virus control, their mode of control is unclear. to gain insight into the possible role of pam in the mediation of avian influenza virus resistance, we compared the host effects and replication of two avian (h2n3 and h6n1) and three mammalian (swine h1n1, human h1n1 and pandemic h1n1) influ ...201526642934
vaccination with soluble headless hemagglutinin protects mice from challenge with divergent influenza viruses.current influenza virus vaccines provide solid protection from infection with viruses that are well matched with the vaccine strains. however, they do not protect efficiently against drifted or shifted strains. we developed an antigen based on the conserved stalk domain of the influenza virus hemagglutinin and tested its efficacy as a vaccine in a mouse virus challenge model. although the antigen lacked the correct conformation of the native stalk domain and was not recognized by a panel of neut ...201526026378
immunization with baculovirus displayed h6 hemagglutinin vaccine protects mice against lethal h6 influenza virus challenge.low pathogenic influenza viruses of h6 hemagglutinin (ha) subtype have a high prevalence among aquatic and domestic birds and have caused outbreaks in poultry worldwide. the first human infection with wild avian influenza h6n1 virus was reported in taiwan and these subtype viruses may continue to evolve and accumulate changes which increasing the potential risk of human-to-human transmission. to develop a vaccine against influenza viruses of the h6 subtype, we displayed the ha gene on the baculo ...201424973759
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
influenza a/hong kong/156/1997(h5n1) virus ns1 gene mutations f103l and m106i both increase ifn antagonism, virulence and cytoplasmic localization but differ in binding to rig-i and cpsf30.the genetic basis for avian to mammalian host switching in influenza a virus is largely unknown. the human a/hk/156/1997 (h5n1) virus that transmitted from poultry possesses ns1 gene mutations f103l + m106i that are virulence determinants in the mouse model of pneumonia; however their individual roles have not been determined. the emergent a/shanghai/patient1/2013(h7n9)-like viruses also possess these mutations which may contribute to their virulence and ability to switch species.201323886034
epidemiological surveillance of low pathogenic avian influenza virus (lpaiv) from poultry in guangxi province, southern china.low pathogenic avian influenza virus (lpaiv) usually causes mild disease or asymptomatic infection in poultry. however, some lpaiv strains can be transmitted to humans and cause severe infection. genetic rearrangement and recombination of even low pathogenic influenza may generate a novel virus with increased virulence, posing a substantial risk to public health. southern china is regarded as the world "influenza epicenter", due to a rash of outbreaks of influenza in recent years. in this study, ...201324204754
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
establishment and lineage replacement of h6 influenza viruses in domestic ducks in southern china.domestic ducks in southern china act as an important reservoir for influenza viruses and have also facilitated the establishment of multiple h6 influenza virus lineages. to understand the continuing evolution of these established lineages, 297 h6 viruses isolated from domestic ducks during 2006 and 2007 were genetically and antigenically analyzed. phylogenetic analyses showed that group ii duck h6 viruses had replaced the previously predominant group i lineage and extended their geographic distr ...201222438558
simultaneous subtyping and pathotyping of avian influenza viruses in chickens in taiwan using reverse transcription loop-mediated isothermal amplification and microarray.the h6n1 avian influenza virus has circulated in taiwan for more than 40 years. the sporadic activity of low pathogenic h5n2 virus has been noted since 2003, and highly pathogenic h5n2 avian influenza virus has been detected since 2008. ressortant viruses between h6n1 and h5n2 viruses have become established and enzootic in chickens throughout taiwan. outbreaks caused by novel highly pathogenic h5 avian influenza viruses whose ha genes were closely related to that of the h5n8 virus isolated from ...201627086860
serological comparison of antibodies to avian influenza viruses, subtypes h5n2, h6n1, h7n3 and h7n9 between poultry workers and non-poultry workers in taiwan in 2012.in taiwan, avian influenza virus (aiv) subtypes h5n2, h6n1 and h7n3 have been identified in domestic poultry, and several strains of these subtypes have become endemic in poultry. to evaluate the potential of avian-to-human transmission due to occupational exposure, an exploratory analysis of aiv antibody status in poultry workers was conducted. we enrolled 670 poultry workers, including 335 live poultry vendors (lpvs), 335 poultry farmers (pfs), and 577 non-poultry workers (npws). serum antibod ...201525761403
emergence and evolution of avian h5n2 influenza viruses in chickens in taiwan.sporadic activity by h5n2 influenza viruses has been observed in chickens in taiwan from 2003 to 2012. the available information suggests that these viruses were generated by reassortment between a mexican-like h5n2 virus and a local enzootic h6n1 virus. yet the origin, prevalence, and pathogenicity of these h5n2 viruses have not been fully defined. following the 2012 highly pathogenic avian influenza (hpai) outbreaks, surveillance was conducted from december 2012 to july 2013 at a live-poultry ...201424623422
origin and molecular characterization of the human-infecting h6n1 influenza virus in taiwan.in june 2013, the first human h6n1 influenza virus infection was confirmed in taiwan. however, the origin and molecular characterization of this virus, a/taiwan/2/2013 (h6n1), have not been well studied thus far. in the present report, we performed phylogenetic and coalescent analyses of this virus and compared its molecular profile/characteristics with other closely related strains. molecular characterization of h6n1 revealed that it is a typical avian influenza virus of low pathogenicity, whic ...201324136722
transforming growth factor-β: activation by neuraminidase and role in highly pathogenic h5n1 influenza pathogenesis.transforming growth factor-beta (tgf-β), a multifunctional cytokine regulating several immunologic processes, is expressed by virtually all cells as a biologically inactive molecule termed latent tgf-β (ltgf-β). we have previously shown that tgf-β activity increases during influenza virus infection in mice and suggested that the neuraminidase (na) protein mediates this activation. in the current study, we determined the mechanism of activation of ltgf-β by na from the influenza virus a/gray teal ...201020949074
insertion of a multibasic cleavage motif into the hemagglutinin of a low-pathogenic avian influenza h6n1 virus induces a highly pathogenic phenotype.the highly pathogenic avian influenza (hpai) virus phenotype is restricted to influenza a viruses of the h5 and h7 hemagglutinin (ha) subtypes. to obtain more information on the apparent subtype-specific nature of the hpai virus phenotype, a low-pathogenic avian influenza (lpai) h6n1 virus was generated, containing an hpai h5 rrrkkr [downward arrow] g multibasic cleavage site (mbcs) motif in ha (the downward arrow indicates the site of cleavage). this insertion converted the lpai virus phenotype ...201020519405
comparison of cloacal and oropharyngeal samples for the detection of avian influenza virus in wild birds.this study was conducted to compare oropharyngeal (op) and cloacal samples of wild birds (n = 137) for the detection and isolation of avian influenza virus (aiv). a total of 39 (28.5%) cloacal and 85 (62.0%) op samples were positive for aiv by real-time reverse transcription-pcr (rrt-pcr). the aiv nucleic acid was detected in both cloacal and op samples from 27 (19.7%) birds, in cloacal samples only from 12 (8.8%) birds, and in op samples only from 58 (42.3%) birds. thus, a total of 97 (70.8%) b ...201020408409
the role of the n-terminal caspase cleavage site in the nucleoprotein of influenza a virus in vitro and in vivo.the n-terminal caspase cleavage in the nucleoprotein (np) of influenza a virus is correlated with the host origin of the virus, thus could be a molecular determinant for host range. we studied how mutations targeting the np cleavage motif of human and avian influenza viruses affect virus replication in vitro and in vivo. the "avian-like" d16-->g substitution in the np, which makes this protein resistant to cleavage, did not significantly affect the human a/puerto rico/8/34 (h1n1) virus replicati ...200818058063
human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals.viral attachment to the host cell is critical for tissue and species specificity of virus infections. recently, pattern of viral attachment (pva) in human respiratory tract was determined for highly pathogenic avian influenza virus of subtype h5n1. however, pva of human influenza viruses and other avian influenza viruses in either humans or experimental animals is unknown. therefore, we compared pva of two human influenza viruses (h1n1 and h3n2) and two low pathogenic avian influenza viruses (h5 ...200717717141
establishment of influenza a virus (h6n1) in minor poultry species in southern china.an h6n1 virus, a/teal/hong kong/w312/97 (w312), was isolated during the "bird flu" incident in hong kong in 1997. genetic analysis suggested that this virus might be the progenitor of the a/hong kong/156/97 (hk/97) h5n1 virus, as seven of eight gene segments of those viruses had a common source. continuing surveillance in hong kong showed that a w312-like virus was prevalent in quail and pheasants in 1999; however, the further development of h6n1 viruses has not been investigated since 2001. her ...200717652385
resistance of immune-suppressed pigeons to subtypes h5n2 and h6n1 low pathogenic avian influenza virus.resistance to infection with avian influenza virus (aiv) was studied in healthy and immune-suppressed pigeons, which were treated with the immunosuppressant cyclophosphamide (cy) before infection. two subtypes of low pathogenic aiv (lpaiv; ck/tw/h5 and ck/tw/h6) were inoculated via the oculonasal route. nested reverse transcriptase-polymerase chain reaction (nested rt-pcr) and virus isolation were used as detection methods. the cy-treated and -untreated pigeons in both experiments did not shed v ...200616863079
[sensitivity of various influenza virus strains to arbidol. influence of arbidol combination with different antiviral drugs on reproduction of influenza virus a].to study antiviral activity of arbidol in relation to various antigenic subtypes of influenza virus isolated from humans; efficacy of arbidol action in combination with adamantanic antiviral drugs, ribavirin and ribamidil on reproduction of influenza virus a (iva) in cell culture.200516206613
avian influenza viruses in korean live poultry markets and their pathogenic potential.we surveyed live-poultry markets in korea in 2003 and isolated 9 h9n2, 6 h3n2, and 1 h6n1 influenza viruses. antigenic and phylogenetic analyses showed that all 9 h9n2 isolates were of a/chicken/korea/25232-96006/96-like lineage (which caused disease in chickens in korea in 1996) but were different from h9n2 viruses of southeastern china. they had at least 4 genotypes and replicated in chickens but not in mice. the h3n2 and h6n1 viruses were new to korea and were probably reassortants of avian i ...200515680418
generation of high-yielding influenza a viruses in african green monkey kidney (vero) cells by reverse genetics.influenza a viruses are the cause of annual epidemics of human disease with occasional outbreaks of pandemic proportions. the zoonotic nature of the disease and the vast viral reservoirs in the aquatic birds of the world mean that influenza will not easily be eradicated and that vaccines will continue to be needed. recent technological advances in reverse genetics methods and limitations of the conventional production of vaccines by using eggs have led to a push to develop cell-based strategies ...200414747549
experimental selection of virus derivatives with variations in virulence from a single low-pathogenicity h6n1 avian influenza virus field isolate.a mixture of viruses with variations in virulence is likely present within a low-pathogenicity avian influenza virus (lpaiv) population. an h6n1 aiv was isolated from a field case showing 3.8% weekly mortality and a 33% egg production drop in taiwan. the pathologic lesions included proventricular hemorrhage and urate deposition in the kidneys and on visceral organs. from the field isolate, a done (2838n) that caused no lesions or death was obtained using limit dilution in chicken embryos and a d ...200314708990
the quest of influenza a viruses for new hosts.there is increasing evidence that stable lineages of influenza viruses are being established in chickens. h9n2 viruses are established in chickens in eurasia, and there are increasing reports of h3n2, h6n1, and h6n2 influenza viruses in chickens both in asia and north america. surveillance in a live poultry market in nanchang, south central china, reveals that influenza viruses were isolated form 1% of fecal samples taken from healthy poultry over the course of 16 months. the highest isolation r ...200314575076
the next influenza pandemic: lessons from hong kong.pandemic influenza is a zoonosis. studies on influenza ecology conducted in hong kong since the 1970s in which hong kong essentially functioned as an influenza sentinel post indicated that it might be possible, for the first time, to have influenza preparedness at the baseline avian level. this appreciation of influenza ecology facilitated recognition of the h5n1 'bird flu' incident in hong kong in 1997 in what was considered to be an incipient pandemic situation, the chicken being the source of ...200312675938
eight-plasmid system for rapid generation of influenza virus vaccines.the antigenic variation of influenza a virus hemagglutinin (ha) and neuraminidase (na) glycoproteins requires frequent changes in vaccine formulation. the classical method of creating influenza virus seed strains for vaccine production is to generate 6 + 2 reassortants that contain six genes from a high-yield virus, such as a/pr/8/34 (h1n1) and the ha and na genes of the circulating strains. the techniques currently used are time-consuming because of the selection process required to isolate the ...200212163268
molecular evolution of h6 influenza viruses from poultry in southeastern china: prevalence of h6n1 influenza viruses possessing seven a/hong kong/156/97 (h5n1)-like genes in poultry.the a/teal/hong kong/w312/97 (h6n1) influenza virus and the human h5n1 and h9n2 influenza viruses possess similar genes encoding internal proteins, suggesting that h6n1 viruses could become novel human pathogens. the molecular epidemiology and evolution of h6 influenza viruses were characterized by antigenic and genetic analyses of 29 h6 influenza viruses isolated from 1975 to 1981 and 1997 to 2000. two distinct groups were identified on the basis of their antigenic characteristics. phylogenetic ...200211752141
characterization of h5n1 influenza viruses that continue to circulate in geese in southeastern china.the h5n1 influenza virus, which killed humans and poultry in 1997, was a reassortant that possibly arose in one type of domestic poultry present in the live-poultry markets of hong kong. given that all the precursors of h5n1/97 are still circulating in poultry in southern china, the reassortment event that generated h5n1 could be repeated. because a/goose/guangdong/1/96-like (h5n1; go/gd) viruses are the proposed donors of the hemagglutinin gene of the h5n1 virus, we investigated the continued c ...200211739677
characterization of the influenza a virus gene pool in avian species in southern china: was h6n1 a derivative or a precursor of h5n1?in 1997, an h5n1 influenza virus outbreak occurred in chickens in hong kong, and the virus was transmitted directly to humans. because there is limited information about the avian influenza virus reservoir in that region, we genetically characterized virus strains isolated in hong kong during the 1997 outbreak. we sequenced the gene segments of a heterogeneous group of viruses of seven different serotypes (h3n8, h4n8, h6n1, h6n9, h11n1, h11n9, and h11n8) isolated from various bird species. the p ...200010864640
replication of avian influenza viruses in humans.volunteers inoculated with avian influenza viruses belonging to subtypes currently circulating in humans (h1n1 and h3n2) were largely refractory to infection. however 11 out of 40 volunteers inoculated with the avian subtypes, h4n8, h6n1, and h10n7, shed virus and had mild clinical symptoms: they did not produce a detectable antibody response. this was presumably because virus multiplication was limited and insufficient to stimulate a detectable primary immune response. avian influenza viruses c ...19911863223
antigen-capture enzyme-linked immunosorbent assays for detection of different h5 avian influenza a virus.avian influenza a virus (aiv) subtype h5 is divided into american and eurasian lineages, according to hemagglutinin gene sequences. although methods for detecting h5 aivs have been described, no h5 strain-specific detection method has been reported. the purpose of the present study was to develop an antigen-capture enzyme-linked immunosorbent assay (ace) to detect and differentiate between the american and the eurasian h5 aivs. monoclonal antibodies (mabs) against the ha fragment of a eurasian h ...201222621946
molecular characterization of h6 subtype influenza viruses in southern china from 2009 to 2011.h6 avian influenza viruses (aivs), which are prevalent in domestic and wild birds in eurasian countries, have been isolated from pigs, a dog and a human. routine virological surveillance at live poultry markets or poultry farms was conducted in southern china from 2009 to 2011. this study investigated the genetic and antigenic characteristics, analyzed the receptor-binding properties and evaluated the kinetics of infectivity of the aivs in a549, mdck and pk15 cells. a total of 14 h6n6 and 2 h6n2 ...201627436363
optical fiber sensor based on surface plasmon resonance for rapid detection of avian influenza virus subtype h6: initial studies.a side-polished fiber optic surface plasmon resonance (spr) sensor was fabricated to expose the core surface and then deposited with a 40 nm thin gold film for the near surface sensing of effective refractive index changes with surface concentration or thickness of captured avian influenza virus subtype h6. the detection surface of the spr optical fiber sensor was prepared through the plasma modification method for binding a self-assembled monolayer of isopropanol chemically on the gold surface ...201626996538
immunochromatographic strip assay development for avian influenza antibody detection.to detect antibody on pen-side is a rapid way to know the avian influenza (ai) infectious status in a chicken flock. the purpose of this study was to develop an immunochromatographic strip (ics) assay to detect the antibody against the ai virus (aiv) for field applications. the ics was constructed by fixing an aiv strain a/chicken/taiwan/2838v/2000 (h6n1) onto a nitrocellulose membrane as the antigen at the test line and goat anti-rabbit igg antibody at the control line. the colloidal gold conju ...201526753244
a novel h6n1 virus-like particle vaccine induces long-lasting cross-clade antibody immunity against human and avian h6n1 viruses.avian influenza a(h6n1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. the first and only known case of human infection by h6n1 virus in the world was reported in taiwan in 2013. this led to concern that h6n1 virus may cause a threat to public health. in this study, we engineered a recombinant h6n1 virus-like particle (vlp) and investigated its vaccine effectiveness compared to the traditional egg-based whole inactivated virus (wiv) ...201626593980
influenza a(h6n1) virus in dogs, taiwan.we determined the prevalence of influenza a virus in dogs in taiwan and isolated a/canine/taiwan/e01/2014. molecular analysis indicated that this isolate was closely related to influenza a(h6n1) viruses circulating in taiwan and harbored the e627k substitution in the polymerase basic 2 protein, which indicated its ability to replicate in mammalian species.201526583707
analysis of viral genetics for estimating diffusion of influenza a h6n1.h6n1 influenza a is an avian virus but in 2013 infected a human in taiwan. we studied the phylogeography of avian origin h6n1 viruses in the influenza research database and the global initiative on sharing avian influenza data epiflu database in order to characterize their recent evolutionary spread. our results suggest that the h6n1 virus that infected a human in taiwan is derived from a diversity of avian strains of h6n1 that have circulated for at least seven years in this region. understandi ...201526306229
structural and functional studies of influenza virus a/h6 hemagglutinin.in june 2013, the first human infection by avian influenza a(h6n1) virus was reported in taiwan. this incident raised the concern for possible human epidemics and pandemics from h6 viruses. in this study, we performed structural and functional investigation on the hemagglutinin (ha) proteins of the human-infecting a/taiwan/2/2013(h6n1) (tw h6) virus and an avian a/chicken/guangdong/s1311/2010(h6n6) (gd h6) virus that transmitted efficiently in guinea pigs. our results revealed that in the presen ...201526226046
novel influenza a (h6n1) virus that infected a person in taiwan. 201426060728
adaptation of avian influenza a (h6n1) virus from avian to human receptor-binding preference.the receptor-binding specificity of influenza a viruses is a major determinant for the host tropism of the virus, which enables interspecies transmission. in 2013, the first human case of infection with avian influenza a (h6n1) virus was reported in taiwan. to gather evidence concerning the epidemic potential of h6 subtype viruses, we performed comprehensive analysis of receptor-binding properties of taiwan-isolated h6 has from 1972 to 2013. we propose that the receptor-binding properties of tai ...201525940072
structure and receptor binding of the hemagglutinin from a human h6n1 influenza virus.avian influenza viruses that cause infection and are transmissible in humans involve changes in the receptor binding site (rbs) of the viral hemagglutinin (ha) that alter receptor preference from α2-3-linked (avian-like) to α2-6-linked (human-like) sialosides. a human case of avian-origin h6n1 influenza virus was recently reported, but the molecular mechanisms contributing to it crossing the species barrier are unknown. we find that, although the h6 ha rbs contains d190v and g228s substitutions ...201525766295
[prediction and evolution of b cell epitopes of hemagglutinin in human-infecting h6n1 avian influenza virus].to predict b cell epitopes of hemagglutinin (ha) of human-infecting h6n1 avian influenza virus and analyze their evolutionary characteristics.201525575051
[adaptive evolution of the hemagglutinin genes of the h6n1 avian influenza virus in taiwan, china].in taiwan, the first human-infecting h6n1 avian influenza virus was isolated in 2013. to better understand the origin, evolutionary relationship and pathogenesis of the h6n1 virus, we studied the adaptive evolution and evolutionary dynamics of the hemagglutinin (ha) genes of the h6n1 virus in taiwan. we felt that such studies woud contribute to the further study and control of the virus. datasets were gained from the flu and global initiative on sharing all influenza data (gisaid) databases. the ...201425562962
glycosylation at hemagglutinin asn-167 protects the h6n1 avian influenza virus from tryptic cleavage at arg-201 and maintains the viral infectivity.cleavage of the hemagglutinin (ha) precursor (ha0) by trypsin, which produces the active ha1 and ha2 complex, is a critical step for activating the avian influenza virus (aiv). however, other tryptic cleavage sites on ha might also cause ha degradation and affect the virulence. otherwise, ha is modified by glycosylation in the host cell. the conjugated glycans on ha may hinder the antigenic epitopes, and thus prevent the virus from being recognized and attacked by the antibodies. in this study, ...201525527464
a monoclonal antibody recognizes a highly conserved neutralizing epitope on hemagglutinin of h6n1 avian influenza virus.neutralizing antibodies on the globular head of the hemagglutinin (ha) of avian influenza virus (aiv) are crucial for controlling this disease. however, most neutralizing antibodies lack cross reaction. this report describes the identification of a hemagglutinin epitope on the globular head near the receptor binding site of the h6n1 aiv. a monoclonal antibody named eb2 was prepared against the h6n1 aiv ha. flow cytometry of aiv-infected chicken embryo fibroblast, df-1 cells and specific-pathogen ...201425465660
multiple amino acid substitutions involved in the adaptation of h6n1 avian influenza virus in mice.h6n1 avian influenza viruses (aivs) are one of the most abundantly detected avian influenza virus subtype, and a human h6n1 infection case has been reported in 2013. h6n1 aivs may pose a potential human risk, however, the factors that promote the replication of h6n1 viruses in mammals remain poorly understood. here, we generated mouse-adapted variants of a h6n1 virus (a/mallard/sanjiang/275/2007) to identify adaptive changes that confer enhanced virulence to h6n1 viruses in mammals. after eight ...201425457364
isolation and genetic characterization of avian influenza virus h4n6 from ducks in china.an avian influenza virus (aiv) strain belonging to the h4 subtype and provisionally designated as a/duck/china/j1/2012(h4n6) was isolated from diseased ducks with respiratory disease at a commercial poultry farm in shandong, china, in 2012. the genomic coding sequences of all eight segments of this j1 isolate were determined and used for subsequent analysis. phylogenetic analysis of all eight segments showed that this duck h4n6 virus was of eurasian lineage and not american lineage. the results ...201525248626
an optimized enzyme-linked lectin assay to measure influenza a virus neuraminidase inhibition antibody titers in human sera.antibodies to neuraminidase (na), the second most abundant surface protein on influenza virus, contribute toward protection against influenza. the traditional thiobarbituric acid (tba) method to quantify na inhibiting antibodies is cumbersome and not suitable for routine serology. an enzyme-linked lectin assay (ella) described by lambre et al. (1990) is a practical alternative method for measuring na inhibition (ni) titers. this report describes optimization of the ella for measuring ni titers i ...201425233882
pb2-e627k and pa-t97i substitutions enhance polymerase activity and confer a virulent phenotype to an h6n1 avian influenza virus in mice.h6n1 avian influenza viruses (aivs) may pose a potential human risk as suggested by the first documented naturally-acquired human h6n1 virus infection in 2013. here, we set out to elucidate viral determinants critical to the pathogenesis of this virus using a mouse model. we found that the recombinant h6n1 viruses possessing both the pa-t97i and pb2-e627k substitutions displayed the greatest enhancement of replication in vitro and in vivo. polymerase complexes possessing either pb2-e627k, pa-t97 ...201425194918
no structural change due to g228s substitution of haemagglutinin in emerging h6n1 influenza virus. 201425183326
anti-influenza virus activity of the ethanolic extract from peperomia sui.peperomia sui lin and lu (peperomia sui), a well-known taiwanese folk medicine, has a broad range of biological effects, especially in treatment of upper respiratory tract diseases. however, no previous study has explored the activity of peperomia sui against influenza virus infections. this study was carried out to evaluate the anti-influenza virus activity and the potential virucidal effect of the ethanolic extract of peperomia sui (pse).201424882727
experimental infection of dogs with h6n1 avian influenza a virus.h6n1 avian influenza a viruses, which have spread across north america, europe and asia, have been shown to be infectious not only for birds but also for mammals. because humans lack immunity to h6n1 avian influenza a viruses, the emergence of these viruses in humans would probably cause a pandemic. replication of h6n1 avian influenza a viruses in dogs may facilitate their adaptation in humans because dogs are often in close contact with humans. however, the susceptibility of dogs to these virus ...201424719193
effect of the pb2 and m genes on the replication of h6 influenza virus in chickens.h6 subtype influenza viruses are commonly isolated from wild aquatic birds. however, limited information is available regarding h6 influenza virus isolated from chickens. we compared the viral genome segment between a/chicken/hong kong/w312/97 (h6n1), which was able to grow in chicken trachea, and a/duck/shantou/5540/01 (h6n2), which was isolated from wild aquatic duck, to explore the factors for effective replication in chicken. when chickens were inoculated with 7 + 1 reassortants (w312 backgr ...201424696782
human infection with avian influenza a h6n1 virus: an epidemiological analysis.avian influenza a h6n1 virus is one of the most common viruses isolated from wild and domestic avian species, but human infection with this virus has not been previously reported. we report the clinical presentation, contact, and environmental investigations of a patient infected with this virus, and assess the origin and genetic characteristics of the isolated virus.201324461756
origin and molecular characteristics of a novel 2013 avian influenza a(h6n1) virus causing human infection in taiwan. 201323881153
a low-pathogenic avian influenza h6n1 outbreak in a turkey flock in france: a comprehensive case report.based on a case observed and investigated on a commercial turkey farm in western france in 81-day-old birds, we report the pattern of h6n1 low-pathogenic avian influenza in this species. diseased birds displayed an acute severe dyspnoea, leading to death by asphyxia of more than 5% of the flock. the most specific pathological feature was a constant diffuse infraorbital sinusitis, along with a focal necrotic exudate inside the lumen of the upper respiratory tract, characterized microscopically as ...201223237370
complete genome sequence analysis of an h6n1 avian influenza virus isolated from guangxi pockmark ducks.we report here the complete genomic sequence of a novel h6n1 avian influenza virus strain, a/duck/guangxi/gxd-5/2010(h6n1), isolated from pockmark ducks in guangxi province, southern china. all of the 8 gene segments of a/duck/guangxi/gxd-5/2010(h6n1) are attributed to the eurasian lineage; the amino acid motif of the cleavage site between ha1 and ha2 was p-q-i-e-t-r-g. these are typical characteristics of the low-pathogenicity avian influenza virus. this study will help to understand the epidem ...201223166266
field monitoring of avian influenza viruses: whole-genome sequencing and tracking of neuraminidase evolution using 454 pyrosequencing.adaptation of avian influenza viruses (aivs) from waterfowl to domestic poultry with a deletion in the neuraminidase (na) stalk has already been reported. the way the virus undergoes this evolution, however, is thus far unclear. we address this question using pyrosequencing of duck and turkey low-pathogenicity aivs. ducks and turkeys were sampled at the very beginning of an h6n1 outbreak, and turkeys were swabbed again 8 days later. na stalk deletions were evidenced in turkeys by sanger sequenci ...201222718944
positive charge of arg-201 on hemagglutinin is required for the binding of h6n1 avian influenza virus to its target through a two-step process.in our previous study, we produced a monoclonal antibody eb2 that recognized an epitope in the ha1 domain on the hemagglutinin (ha) of h6n1 influenza virus (a/chicken/taiwan/2838 v/00). the residue arg-201 (r201) on this epitope was protected by the glycan at asn-167 (n167) from tryptic digestion; therefore, the infectivity of the virus was retained. r201 was extremely conserved in various subtypes of the influenza virus. to explore the role of r201 and the protecting glycan, we developed a bi-c ...201930926385
isolation and characterization of novel reassortant h6n1 avian influenza viruses from chickens in eastern china.the h6n1 subtype of avian influenza viruses (aivs) can infect people with an influenza-like illness; the h6n1 viruses possess the ability for zoonotic transmission from avians into mammals, and possibly pose a threat to human health.201830355336
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