Publications

TitleAbstractYear
Filter
PMID(sorted ascending)
Filter
an influenza a (h1n1) virus, closely related to swine influenza virus, responsible for a fatal case of human influenza.in july 1991, an influenza a virus, designated a/maryland/12/91 (a/md), was isolated from the bronchial secretions of a 27-year-old animal caretaker. he had been admitted to the hospital with bilateral pneumonia and died of acute respiratory distress syndrome 13 days later. antigenic analyses with postinfection ferret antisera and monoclonal antibodies to recent h1 swine hemagglutinins indicated that the hemagglutinin of this virus was antigenically related to, but distinguishable from, those of ...19948138990
comparison of influenza serological techniques by international collaborative study.an international collaborative study was performed to investigate the reproducibility of influenza serological techniques. participants in seven laboratories representing five countries measured antibody to a/sichuan/2/87 (h3n2), a/taiwan/1/86 (h1n1) and b/beijing/1/87 influenza viruses in 11 human sera and three postinfection ferret sera. two different serological techniques were used, haemagglutination inhibition (hi) and single-radial haemolysis (srh) and, although each technique was reproduc ...19948147099
effect of simultaneous administration of cold-adapted and wild-type influenza a viruses on experimental wild-type influenza infection in humans.on the basis of the ability of the attenuated cold-adapted strain of influenza a virus to suppress disease production in ferrets simultaneously infected with epidemic influenza virus (p. whitaker-dowling, h.f. maassab, and j.s. youngner, j. infect. dis. 164:1200-1202, 1991), an evaluation of the ability of the cold-adapted virus to modify clinical disease in humans was made. adult volunteers with prechallenge serum hemagglutination-inhibition titers to the influenza a/kawasaki/86 (h1n1) virus of ...19948195389
efficacy of equine influenza vaccines for protection against a/equine/jilin/89 (h3n8)--a new equine influenza virus.a new h3n8 equine influenza virus [a/equine/jilin/1/89 (eq/jilin)] appeared in northeastern china in 1989 and caused high mortality in horses; the available evidence indicates that it has not yet spread outside this region of the world. serological analysis with postinfection ferret sera in haemagglutination inhibition (hi) tests confirmed that eq/jilin is antigenically distinct from h3n8 equine influenza viruses isolated between 1963 and 1991 and also showed that a current equine influenza viru ...19938212831
host-specific hemagglutination of influenza a (h1n1) virus.h1n1 strains of influenza a virus isolated during the influenza season of 1991-92 were divided into two groups according to the property of host-specific hemagglutination. group 1 viruses agglutinated human and chicken red blood cells. group 2 viruses agglutinated human but not chicken red blood cells. the viruses of both groups, however, showed the same antigenic structure determined with ferret antisera. the virus clones which were plaque-purified twice from a group 2 virus retained the charac ...19938246828
influence of host cell-mediated variation on the international surveillance of influenza a (h3n2) viruses.growth of clinical specimens of influenza viruses in eggs can result in the selection of antigenic variants distinct from corresponding viruses grown in mammalian tissue culture. to evaluate the contribution of host cell selection on the antigenic diversity of human influenza isolates, as seen in annual surveillance studies, viruses grown in embryonated eggs were compared by antigenic and genetic analyses with their mammalian tissue culture-grown counterparts. clinical specimens were gathered fr ...19938356790
antibody response to the m2 protein of influenza a virus expressed in insect cells.a recombinant baculovirus expressing the m2 protein from influenza a/ann arbor/6/60 (h2n2) virus (aa60 virus) was constructed. the expressed m2 protein was recognized by a monoclonal antibody specific for the m2 protein and comigrated with the m2 protein from cells infected with aa60 virus on sds-polyacrylamide gels. immunofluorescence studies indicated that the expressed m2 protein was present on the surface of spodoptera frugiperda (sf9) cells infected with the recombinant baculovirus. immunoa ...19938423445
receptor specificity of influenza virus influences severity of illness in ferrets.weanling ferrets were inoculated intranasally with either wild-type or receptor-variant clones of influenza a/memphis/102/72 to determine if changes in receptor specificity influence virulence of influenza virus infection. over the 5 days after inoculation, receptor-variant inoculated ferrets had a lower mean elevation in body temperature, greater weight gain and less sneezing than the wild-type group. influenza virus was recovered from the lungs of fewer receptor-variant infected ferrets (5/12 ...19958578828
gg167 (4-guanidino-2,4-dideoxy-2,3-dehydro-n-acetylneuraminic acid) is a potent inhibitor of influenza virus in ferrets.gg167 (4-guanidino-2,4-dideoxy-2,3-dehydro-n-acetylneuraminic acid) is a novel viral neuraminidase (sialidase) inhibitor which, following intranasal administration in ferrets, is at least 100 to 1,000 times more effective than ribavirin and amantadine against influenza a and b viruses. it retains its activity even when treatments are delayed until 24 h postinfection and has no effect on the serum antibody response to infection.19958585752
temperature sensitive mutants of influenza a virus generated by reverse genetics and clustered charged to alanine mutagenesis.temperature sensitive (ts) mutants of influenza a virus have the potential to serve as live attenuated (att) virus vaccines. previously, ts mutants were isolated by chemical mutagenesis or arose spontaneously, and most likely contained point mutations in one or more genes. while sufficiently attenuated, even the most genetically stable of these viruses was found to revert to a more virulent form in a seronegative vaccinee. recently developed technology, however, allows the introduction of engine ...19969029775
genetically engineered live attenuated influenza a virus vaccine candidates.we have generated new influenza a virus live attenuated vaccine candidates by site-directed mutagenesis and reverse genetics. by mutating specific amino acids in the pb2 polymerase subunit, two temperature-sensitive (ts) attenuated viruses were obtained. both candidates have 38 degrees c shutoff temperatures in mdck cells, are attenuated in the respiratory tracts of mice and ferrets, and have very low reactogenicity in ferrets. infection of mice or ferrets with either mutant conferred significan ...19979060631
the cysteine residues of the m2 protein are not required for influenza a virus replication.the m2 protein of influenza a virus functions as an ion channel. it contains three cysteine residues: cysteines 17 and 19, which form disulfide bonds in the ectodomain, and cysteine 50 which is acylated. to understand the role of these cysteine residues in virus replication, we used reverse genetics to create influenza viruses in which the individual cysteines were mutated and a virus in which all three cysteines were changed to serine. the m2 cysteine mutants that lacked either of the cysteine ...19979375016
oral administration of a prodrug of the influenza virus neuraminidase inhibitor gs 4071 protects mice and ferrets against influenza infection.we have recently described gs 4071, a carbocyclic transition-state analog inhibitor of the influenza virus neuraminidase, which has potent inhibitory activity comparable to that of 4-guanidino-neu5ac2en (gg167; zanamivir) when tested against influenza a virus replication and neuraminidase activity in vitro. we now report that gs 4071 is active against several strains of influenza a and b viruses in vitro and that oral gs 4104, an ethyl ester prodrug which is converted to gs 4071 in vivo, is acti ...19989517945
identification of gs 4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor gs 4071.gs 4071 is a potent carbocyclic transition-state analog inhibitor of influenza virus neuraminidase with activity against both influenza a and b viruses in vitro. gs 4116, the guanidino analog of gs 4071, is a 10-fold more potent inhibitor of influenza virus replication in tissue culture than gs 4071. in this study we determined the oral bioavailabilities of gs 4071, gs 4116, and their respective ethyl ester prodrugs in rats. both parent compounds and the prodrug of the guanidino analog exhibited ...19989517946
zanamivir.zanamivir is the first of a new class of selective influenza virus neuraminidase inhibitors. it inhibits both influenza a and influenza b virus replication in vitro. in the ferret model of influenza, zanamivir reduced viral replication and diminished pyrexia associated with the infection. repeated passage of influenza virus in the presence of zanamivir could produce resistance in vitro. however, there have been no changes in sensitivity to zanamivir in any influenza virus isolates from patients ...19989585868
recombinant influenza a virus vaccines for the pathogenic human a/hong kong/97 (h5n1) viruses.recombinant reassortment technology was used to prepare h5n1 influenza vaccine strains containing a modified hemagglutinin (ha) gene and neuraminidase gene from the a/hong kong/156/97 and a/hong kong/483/97 isolates and the internal genes from the attenuated cold-adapted a/ann arbor/6/60 influenza virus strain. the ha cleavage site (ha1/ha2) of each h5n1 isolate was modified to resemble that of "low-pathogenic" avian strains. five of 6 basic amino acids at the cleavage site were deleted, and a t ...199910191214
chemoprophylaxis of influenza a virus infections, with single doses of zanamivir, demonstrates that zanamivir is cleared slowly from the respiratory tract.zanamivir (4-guanidino-2,4-dideoxy-2,3-dehydro-n-acetylneuraminic acid; relenza; gg167) is a potent and highly specific neuraminidase (sialidase) inhibitor with inhibitory activity in vivo against both influenza a and b viruses. this compound has been extensively tested in both mouse and ferret models of influenza and has recently been approved for the treatment of influenza in europe and australasia. the compound markedly reduces the clinical course of disease in humans when given therapeutical ...199910543741
oseltamivir.oseltamivir is the oral prodrug of gs4071, a selective inhibitor of influenza a and b viral neuraminidase. after absorption from the gastrointestinal tract oseltamivir is efficiently converted to gs4071, which is maintained at high and sustained concentrations in plasma. based on studies in rats and ferrets, gs4071 appears to be effectively distributed to all tissues, including major sites of infection in the upper and lower respiratory tracts. oral oseltamivir was an effective treatment in natu ...199910595865
zanamivir susceptibility monitoring and characterization of influenza virus clinical isolates obtained during phase ii clinical efficacy studies.zanamivir is a highly selective neuraminidase (na) inhibitor with demonstrated clinical efficacy against influenza a and b virus infections. in phase ii clinical efficacy trials (naib2005 and naib2008), virological substudies showed mean reductions in virus shedding after 24 h of treatment of 1.5 to 2.0 log(10) 50% tissue culture infective doses compared to a placebo, with no reemergence of virus after the completion of therapy. paired isolates (n = 41) obtained before and during therapy with za ...200010602727
immunological effects of the orally administered neuraminidase inhibitor oseltamivir in influenza virus-infected and uninfected mice.oseltamivir (gs4104), the ethyl ester prodrug of the carbocyclic transition state sialic acid analog gs4071, has been reported to be a striking inhibitor of influenza a and b virus infections in mice and ferrets. multiple studies indicate this material to also be active against the disease in humans, and it has recently been approved for human use. the effect of oral gavage (p.o.) therapy of oseltamivir on various immune factors considered to be of importance in primary influenza virus infection ...200010708809
mismatch between the 1997/1998 influenza vaccine and the major epidemic a(h3n2) virus strain as the cause of an inadequate vaccine-induced antibody response to this strain in the elderly.the success of influenza vaccination depends largely on the antigenic match between the influenza vaccine strains and the virus strains actually circulating during the season. in the past, this match has proved to be satisfactory in most seasons. in the 1997/1998 season, however, hemagglutination inhibition (hi) assays with ferret antisera indicated a considerable mismatch between the h3n2 vaccine component and the most prevalent epidemic influenza a(h3n2) virus. the results from antigenic analy ...200010745239
dna vaccination against influenza viruses: a review with emphasis on equine and swine influenza.the influenza virus vaccines that are commercially-available for humans, horses and pigs in the united states are inactivated, whole-virus or subunit vaccines. while these vaccines may decrease the incidence and severity of clinical disease, they do not consistently provide complete protection from virus infection. dna vaccines are a novel alternative to conventional vaccination strategies, and offer many of the potential benefits of live virus vaccines without their risks. in particular, becaus ...200010799787
ferret respiratory diseases.ferret behavior often brings them into close contact with potential respiratory pathogens and traumatic insults. although respiratory disease accounts for a small percentage of cases, they are usually dramatic. acute and chronic conditions occur, and many lesions are confined to the upper or lower respiratory tree but may not involve both. pathogens such as influenza a account for a large percentage of upper respiratory infections and often mirror the "flu" season of humans. traumatic insults to ...200011228888
serum amyloid p component inhibits influenza a virus infections: in vitro and in vivo studies.serum amyloid p component (sap) binds in vitro ca(2+)-dependently to several ligands including oligosaccharides with terminal mannose and galactose. we have earlier reported that sap binds to human influenza a virus strains, inhibiting hemagglutinin (ha) activity and virus infectivity in vitro. these studies were extended to comprise five mouse-adapted influenza a strains, two swine influenza a strains, a mink influenza a virus, a ferret influenza a reassortant virus, a influenza b virus and a p ...200111530187
pathogenesis of avian influenza a (h5n1) viruses in ferrets.highly pathogenic avian influenza a h5n1 viruses caused outbreaks of disease in domestic poultry and humans in hong kong in 1997. direct transmission of the h5n1 viruses from birds to humans resulted in 18 documented cases of respiratory illness, including six deaths. here we evaluated two of the avian h5n1 viruses isolated from humans for their ability to replicate and cause disease in outbred ferrets. a/hong kong/483/97 virus was isolated from a fatal case and was highly pathogenic in the balb ...200211932409
dna vaccination of ferrets with chimeric influenza a virus hemagglutinin (h3) genes.recently a technology was established based on homologous recombination that allowed the rapid generation of chimeric ha genes of influenza viruses, containing the antigenic determinants obtained from various influenza virus a (h3n2) viruses. in the present report plasmids were generated using a h3 ha vector handle and the hypervariable regions of two genetically distinct influenza a h3n2 viruses, a/stockholm/7/97 and a/netherlands/18/94. in a ferret model it was shown that immunisation with pla ...200211972972
peramivir (bcx-1812, rwj-270201): potential new therapy for influenza.the cyclopentane peramivir (bcx-1812, rwj-270201) is a highly selective inhibitor of influenza a and b virus neuraminidases and a potent inhibitor of influenza a and b virus replication in cell culture. the in vitro potency appears to be greater than either zanamivir or oseltamivir carboxylate based on the generally lower ec(50) values seen using peramivir in studies run in parallel with each compound. in mice infected with influenza a or b viruses, oral treatment with peramivir was highly effec ...200212036429
influenza virus carrying neuraminidase with reduced sensitivity to oseltamivir carboxylate has altered properties in vitro and is compromised for infectivity and replicative ability in vivo.oseltamivir phosphate (tamiflu, ro 64-0796) is the first orally administered neuraminidase (na) inhibitor approved for use in treatment and prevention of influenza virus infection in man. oseltamivir phosphate is the pro-drug of the active metabolite oseltamivir carboxylate (ro 64-0802). extensive monitoring throughout the oseltamivir development programme has identified a very low incidence of patients who have carried drug-resistant virus. the predominant mutation seen is the substitution of a ...200212062393
the h274y mutation in the influenza a/h1n1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo.oseltamivir carboxylate is a potent and specific inhibitor of influenza a and b neuraminidase (na). oseltamivir phosphate, the ethyl ester prodrug of oseltamivir carboxylate, is the first orally active na inhibitor available for the prophylaxis and treatment of influenza a and b. it offers an improvement over amantadine and rimantadine which are active only against influenza a and rapidly generate resistant virus. the emergence of virus resistant to oseltamivir carboxylate in the treatment of na ...200212103431
characterization of 2 influenza a(h3n2) clinical isolates with reduced susceptibility to neuraminidase inhibitors due to mutations in the hemagglutinin gene.previous studies have shown that amino acid changes in the hemagglutinin (ha) gene of influenza viruses may result in decreased susceptibility to neuraminidase inhibitors (nais) in vitro. however, the emergence and characteristics of such ha variants in the clinical setting remain poorly studied. herein, we report 2 influenza a(h3n2) isolates, from untreated patients, harboring an arg229-->ile substitution in the ha1 gene. the ile229 variants were as sensitive as the arg229 viruses to zanamivir ...200212355356
an evaluation of the genetic stability and pathogenicity of the russian cold-adapted influenza a donor strains a/leningrad/134/17/57 and a/leningrad/134/47/57 in ferrets.the influenza a components of live attenuated vaccines used in russia have been prepared as reassortants of the cold-adapted (ca) h2n2 viruses, a/leningrad/134/17/57-ca (len/17) and a/leningrad/134/47/57-ca (len/47), and virulent epidemic strains. the lesions responsible for attenuation within the six internal genes of each donor strain have been sequenced and described, but relatively little is known as to their stability before and after passage in susceptible hosts. in the work reported in th ...200312445939
pathogenicity and antigenicity of a new influenza a (h5n1) virus isolated from duck meat.avian influenza a viruses are the ancestral origin of all human influenza viruses. the outbreak of highly pathogenic (hp) avian h5n1 in hong kong in 1997 highlighted the potential of these viruses to infect and cause severe disease in humans. since 1999, hp h5n1 viruses were isolated several times from domestic poultry in asia. in 2001, a hp h5n1 virus, a/duck/anyang/avl-1/2001 (dk/anyang), was isolated from imported frozen duck meat in korea. because of this novel source of hp h5n1 virus isolat ...200312601764
tissue tropism of a strain of influenza a virus in ferrets. 195513233518
antigenic variants of influenza a virus (pr8 strain). v. virulence, antigenic potency, and cross-protection tests in mice of the original and second series.two series of variants of influenza pr8-s virus have been described. while all retain the same degree of pathogenicity for mice and fertile eggs, there was a progressive loss in the ability of the variants to provoke antibody following vaccination or infection of mice and ferrets. the immunogenicity of the variants was, therefore, less than that of the original strain. although little or no serological relationship could be demonstrated between some of the variants and the pr8-s virus a consider ...195813539310
[studies on the virusemia in ferrets infected with the influenza virus a-1]. 196414198514
studies on influenza infection in ferrets by means of fluorescein-labelled antibody. ii. the role of soluble antigen in nuclear fluorescence and cross-reactions.yellow-green fluorescence representing viral antigens was detected in both the nucleus and cytoplasm of epithelial cells of the respiratory tract in ferrets infected with influenza virus. this nuclear fluorescence was the chief manifestation of cross-fluorescent staining reactions among three strains of influenza a virus studied, pr8, farrington, and fm(1). absorption experiments with influenza viral v and soluble s antigens showed that s antigen was responsible for the presence of fluorescence ...195514367688
neurological manifestations of avian influenza viruses in mammals.the h5n1 viruses isolated from humans in hong kong directly infected both mice and ferrets without prior adaptation to either host. two representative viruses, a/hong kong/483/97 (hk/483) and a/hong kong/486/97 (hk/486) were equally virulent in outbred ferrets but differed in their virulence in inbred mice. both hk/483 and hk/486 replicated systemically in ferrets and showed neurologic manifestations. in contrast, intranasal infection of mice with hk/483, but not hk/486, resulted in viral spread ...200314575126
pathogenesis of and immunity to a new influenza a (h5n1) virus isolated from duck meat.the outbreak of avian influenza h5n1 in hong kong in 1997 raised concerns about the potential for the h5 subtype to cause a human pandemic. in 2001 a new h5n1 virus, a/duck meat/anyang/avl-1/2001 (a/dkmt), was isolated from imported duck meat in korea. the pathogenesis of this virus was investigated in mice. a/dkmt virus had low infectivity but was lethal for mice at high doses, and at lethal doses, the virus replicated in the brains of infected mice. a/dkmt virus cross-reacted poorly with ferre ...200314575129
assessment of development of resistance to antivirals in the ferret model of influenza virus infection.we attempted to develop in vivo resistance of influenza virus to amantadine and to zanamivir, by use of the ferret model of influenza virus infection. resistance of influenza virus a/losangeles/1/87 (h3n2) to amantadine was generated within 6 days, during a single course of treatment, and mutations in the m2 gene that are characteristic of human infections were observed. in contrast, during an identical single course of treatment with zanamivir, no evidence of reduced susceptibility was demonstr ...200314593594
imparting temperature sensitivity and attenuation in ferrets to a/puerto rico/8/34 influenza virus by transferring the genetic signature for temperature sensitivity from cold-adapted a/ann arbor/6/60.the four temperature-sensitive (ts) loci identified in the pb1 and pb2 gene segments of cold-adapted a/ann arbor/6/60 influenza virus, the master donor virus for influenza a virus (mdv-a) flumist vaccines, were introduced into a divergent a/puerto rico/8/34 influenza virus strain. recombinant a/puerto rico/8/34 virus with these four introduced ts loci exhibited both ts and att phenotypes similar to those of mdv-a, which could be used as a donor virus for manufacturing large quantities of inactiv ...200414694130
adrenocorticotrophic hormone (acth) in the treatment of experimental air-borne influenza virus type a infection in the ferret. 195114824691
pathogenicity and immunogenicity of influenza viruses with genes from the 1918 pandemic virus.the 1918 influenza a h1n1 virus caused the worst pandemic of influenza ever recorded. to better understand the pathogenesis and immunity to the 1918 pandemic virus, we generated recombinant influenza viruses possessing two to five genes of the 1918 influenza virus. recombinant influenza viruses possessing the hemagglutinin (ha), neuraminidase (na), matrix (m), nonstructural (ns), and nucleoprotein (np) genes or any recombinant virus possessing both the ha and na genes of the 1918 influenza virus ...200414963236
live cold-adapted influenza a vaccine produced in vero cell line.the african green monkey kidney (vero) cell line was used as a substrate for the development of a live cold-adapted (ca) reassortant influenza vaccine. for that purpose, a new master strain was generated by an adaptation of the wild type (wt) a/singapore/1/57 virus to growth at 25 degrees c in a vero cell line. the resulting cold-adapted (ca) muster strain a/singapore/1/57ca showed temperature sensitive (ts) phenotype and was attenuated in animal models and protective in the challenge experiment ...200415163508
preclinical study of influenza virus a m2 peptide conjugate vaccines in mice, ferrets, and rhesus monkeys.a universal influenza virus vaccine that does not require frequent updates and/or annual immunizations will offer significant advantages over current seasonal flu vaccines. the highly conserved influenza virus a m2 membrane protein has been previously suggested as a potential antigen target for such a vaccine. here, we report systematic evaluation of m2 peptide conjugate vaccines (synthetic peptides of m2 extracellular domain conjugated to keyhole limpet hemocyanin (klh) or neisseria meningitidi ...200415297047
protective efficacy of intranasal cold-adapted influenza a/new caledonia/20/99 (h1n1) vaccines comprised of egg- or cell culture-derived reassortants.live, cold-adapted, temperature-sensitive (ca/ts) russian influenza a vaccines are prepared in eggs by a 6:2 gene reassortment of the ca/ts donor strain a/leningrad/134/17/57 (h2n2) (len/17) with a current wild-type (wt) influenza a strain contributing hemagglutinin (ha) and neuraminidase (na) genes. however, egg-derived reassortant vaccines are potentially more problematic to manufacture in large quantities than vaccines from cell-based procedures. to compare egg- and cell culture-derived reass ...200415351492
influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets.three type a influenza viruses, each of which has a distinct neuraminidase-gene mutation and is resistant to the neuraminidase inhibitor oseltamivir, have been isolated. previously, in the ferret model, an r292k mutant of a type a (h3n2) virus was not transmitted under conditions in which the wild-type virus was transmitted. this model was used to investigate whether the e119v mutant of a type a (h3n2) virus and the h274y mutant of a type a (h1n1) virus would be transmitted under similar circums ...200415478068
predicting antigenic variants of influenza a/h3n2 viruses.current inactivated influenza vaccines provide protection when vaccine antigens and circulating viruses share a high degree of similarity in hemagglutinin protein. five antigenic sites in the hemagglutinin protein have been proposed, and 131 amino acid positions have been identified in the five antigenic sites. in addition, 20, 18, and 32 amino acid positions in the hemagglutinin protein have been identified as mouse monoclonal antibody-binding sites, positively selected codons, and substantiall ...200415496238
viral diseases of ferrets.distemper and rabies vaccination are highly recommended because of the almost invariable fatal outcome of these conditions. vaccination should constitute an important part of a ferret's preventative medicine program. with the current and anticipated development and licensing of new vaccines, practitioners are invited to gain awareness of the latest vaccine information. establishment of a practice vaccination protocol with regards to the site of administration of rabies and distemper vaccines is ...200515585193
lethality to ferrets of h5n1 influenza viruses isolated from humans and poultry in 2004.the 2004 outbreaks of h5n1 influenza viruses in vietnam and thailand were highly lethal to humans and to poultry; therefore, newly emerging avian influenza a viruses pose a continued threat, not only to avian species but also to humans. we studied the pathogenicity of four human and nine avian h5n1/04 influenza viruses in ferrets (an excellent model for influenza studies). all four human isolates were fatal to intranasally inoculated ferrets. the human isolate a/vietnam/1203/04 (h5n1) was the mo ...200515681421
isolation and characterization of avian influenza viruses, including highly pathogenic h5n1, from poultry in live bird markets in hanoi, vietnam, in 2001.since 1997, outbreaks of highly pathogenic (hp) h5n1 and circulation of h9n2 viruses among domestic poultry in asia have posed a threat to public health. to better understand the extent of transmission of avian influenza viruses (aiv) to humans in asia, we conducted a cross-sectional virologic study in live bird markets (lbm) in hanoi, vietnam, in october 2001. specimens from 189 birds and 18 environmental samples were collected at 10 lbm. four influenza a viruses of the h4n6 (n = 1), h5n2 (n = ...200515767421
protection afforded by intranasal immunization with the neuraminidase-lacking mutant of influenza a virus in a ferret model.protective efficacy of the intranasal immunization with the neuraminidase (na)-deficient mutant of the influenza a virus was investigated in ferrets. despite the highly attenuated replication in vivo, the mutant completely protected the animals against the wild type virus challenge. when challenge was done with antigenic drift variants, significant reductions in the viral titers, inflammatory cell counts, and protein concentrations were observed in the nasal washes of the immunized animals. the ...200515780741
characterisation of three equine influenza a h3n8 viruses from germany (2000 and 2002): evidence for frozen evolution.reported here are the results of antigenic and genetic characterisation of equine influenza strains causing local outbreaks reported to the equine diagnostic centre in berlin, germany. in 2000, equine influenza virus was detected in a nasal swab from a non-vaccinated horse using a rapid diagnostic kit, but was not successfully isolated. partial direct sequencing of the haemagglutinin (ha1) gene, indicated that the virus was a european lineage h3n8 subtype strain representative of strains isolate ...200515795074
characterization of a human h5n1 influenza a virus isolated in 2003.in 2003, h5n1 avian influenza virus infections were diagnosed in two hong kong residents who had visited the fujian province in mainland china, affording us the opportunity to characterize one of the viral isolates, a/hong kong/213/03 (hk213; h5n1). in contrast to h5n1 viruses isolated from humans during the 1997 outbreak in hong kong, hk213 retained several features of aquatic bird viruses, including the lack of a deletion in the neuraminidase stalk and the absence of additional oligosaccharide ...200516014953
[clue to the molecular mechanism of virulence of highly pathogenic h5n1 avian influenza viruses isolated in 2004].highly pathogenic avian h5n1 influenza a viruses have spread throughout asia since 2003. these viruses are highly lethal to birds and humans. of the 74 confirmed human cases, 49 were fatal (as of mar 30, 2005), raising concerns of a possible pandemic by these viruses. despite the well-established pathogenicity of these viruses, the molecular mechanism for expressing such high virulence remains elusive. thus, we examined the pathogenicity of the h5n1 viruses isolated in vietnam in 2003-2004 using ...200516308530
avian influenza and the brain--comments on the occasion of resurrection of the spanish flu virus.recent incidences of direct passage of highly pathogenic avian influenza a virus strains of the h5n1 and h7n7 subtypes from birds to man have become a major public concern. although presence of virus in the human brain has not yet been reported in deceased patients, these avian influenza subtypes have the propensity to invade the brain along cranial nerves to target brainstem and diencephalic nuclei following intranasal instillation in mice and ferrets. the associations between influenza and psy ...200616459194
quantifying influenza vaccine efficacy and antigenic distance.we introduce a new measure of antigenic distance between influenza a vaccine and circulating strains. the measure correlates well with efficacies of the h3n2 influenza a component of the annual vaccine between 1971 and 2004, as do results of a theory of the immune response to influenza following vaccination. this new measure of antigenic distance is correlated with vaccine efficacy to a greater degree than are current state of the art phylogenetic sequence analyses or ferret antisera inhibition ...200616460844
h5n1 virus attachment to lower respiratory tract.highly pathogenic avian influenza virus (h5n1) may cause severe lower respiratory tract (lrt) disease in humans. however, the lrt cells to which the virus attaches are unknown for both humans and other mammals. we show here that h5n1 virus attached predominantly to type ii pneumocytes, alveolar macrophages, and nonciliated bronchiolar cells in the human lrt, and this pattern was most closely mirrored in cat and ferret tissues. these findings may explain, at least in part, the localization and se ...200616556800
sialidase fusion protein as a novel broad-spectrum inhibitor of influenza virus infection.influenza is a highly infectious disease characterized by recurrent annual epidemics and unpredictable major worldwide pandemics. rapid spread of the highly pathogenic avian h5n1 strain and escalating human infections by the virus have set off the alarm for a global pandemic. to provide an urgently needed alternative treatment modality for influenza, we have generated a recombinant fusion protein composed of a sialidase catalytic domain derived from actinomyces viscosus fused with a cell surface ...200616569867
influenza virus infections in mammals.the natural reservoir of all known subtypes of influenza a viruses are aquatic birds, mainly of the orders anseriformes and charadriiformes in which the infection is asymptomatic and the viruses stay at an evolutionary equilibrium. however, mammals may occasionally contract influenza a virus infections from this pool. this article summarizes: (i) natural infections in mammals including pigs, horses, marine mammals, ferrets, minks; (ii) results from experimental infections in several animal model ...200616573202
interfering vaccine (defective interfering influenza a virus) protects ferrets from influenza, and allows them to develop solid immunity to reinfection.defective interfering (di) virus rnas result from major deletions in full-length viral rnas that occur spontaneously during de novo rna synthesis. these rnas are packaged into virions that are by definition non-infectious, and are delivered to cells normally targeted by the virion. di rnas can only replicate with the aid of a coinfecting infectious helper virus, but the small size of di rna allows more copies of it to be made than of its full-length counterpart, so the cell produces defective vi ...200616621180
bacterial sinusitis and otitis media following influenza virus infection in ferrets.streptococcus pneumoniae is the leading cause of otitis media, sinusitis, and pneumonia. many of these infections result from antecedent influenza virus infections. in this study we sought to determine whether the frequency and character of secondary pneumococcal infections differed depending on the strain of influenza virus that preceded bacterial challenge. in young ferrets infected with influenza virus and then challenged with pneumococcus, influenza viruses of any subtype increased bacterial ...200616622191
lack of transmission of h5n1 avian-human reassortant influenza viruses in a ferret model.avian influenza a h5n1 viruses continue to spread globally among birds, resulting in occasional transmission of virus from infected poultry to humans. probable human-to-human transmission has been documented rarely, but h5n1 viruses have not yet acquired the ability to transmit efficiently among humans, an essential property of a pandemic virus. the pandemics of 1957 and 1968 were caused by avian-human reassortant influenza viruses that had acquired human virus-like receptor binding properties. ...200616880383
live, attenuated influenza a h5n1 candidate vaccines provide broad cross-protection in mice and ferrets.recent outbreaks of highly pathogenic influenza a h5n1 viruses in humans and avian species that began in asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic.200616968127
cross-protectiveness and immunogenicity of influenza a/duck/singapore/3/97(h5) vaccines against infection with a/vietnam/1203/04(h5n1) virus in ferrets.ferrets were immunized with two 7- mu g doses of hemagglutinin from inactivated whole-virus vaccines containing the hemagglutinin gene of a/duck/singapore/3/97(h5n3) then inoculated with a lethal dose of a/vietnam/1203/04(h5n1) (viet/1203/04). serum samples did not react with viet/1203/04 in hemagglutination-inhibition (hi) or virus-neutralization (vn) tests. all vaccinated ferrets survived the challenge, whereas all mock-immunized ferrets died. immunized ferrets had significantly lower virus ti ...200616991078
highly pathogenic avian influenza h5n1 virus in cats and other carnivores.the asian lineage highly pathogenic avian influenza (hpai) h5n1 virus is a known pathogen of birds. only recently, the virus has been reported to cause sporadic fatal disease in carnivores, and its zoonotic potential has been dominating the popular media. attention to felids was drawn by two outbreaks with high mortality in tigers, leopards and other exotic felids in thailand. subsequently, domestic cats were found naturally infected and experimentally susceptible to h5n1 virus. a high susceptib ...200717250978
evaluation of influenza virus-like particles and novasome adjuvant as candidate vaccine for avian influenza.the development of safe and effective vaccines for avian influenza viruses is a priority for pandemic preparedness. adjuvants improve the efficacy of vaccines and may allow antigen sparing during a pandemic. we have previously shown that influenza virus-like particles (vlps) comprised of ha, na, and m1 proteins represent a candidate vaccine for avian influenza h9n2 virus [pushko p, tumpey tm, fang bu, knell j, robinson r, smith g. influenza virus-like particles comprised of the ha, na, and m1 pr ...200717403562
comparison of neutralising antibody assays for detection of antibody to influenza a/h3n2 viruses: an international collaborative study.a study was performed to investigate the reproducibility of haemagglutinin-inhibition (hi) and virus neutralising (vn) assays for detection of anti-influenza antibody. participants in 11 laboratories from eight countries measured antibody to egg-grown a/japan/434/2003, cell-grown a/japan/434/2003 and a/panama/2007/99 (h3n2) viruses in 18 human and two post-infection ferret sera. there was significant intra-laboratory assay variability for vn compared to hi. for replicate assays within laboratori ...200717412461
inefficient transmission of h5n1 influenza viruses in a ferret contact model.the abilities to infect and transmit efficiently among humans are essential for a novel influenza a virus to cause a pandemic. to evaluate the pandemic potential of widely disseminated h5n1 influenza viruses, a ferret contact model using experimental groups comprised of one inoculated ferret and two contact ferrets was used to study the transmissibility of four human h5n1 viruses isolated from 2003 to 2006. the effects of viral pathogenicity and receptor binding specificity (affinity to syntheti ...200717459930
low ph gel intranasal sprays inactivate influenza viruses in vitro and protect ferrets against influenza infection.developing strategies for controlling the severity of pandemic influenza is a global public health priority. in the event of a pandemic there may be a place for inexpensive, readily available, effective adjunctive therapies to support containment strategies such as prescription antivirals, vaccines, quarantine and restrictions on travel. inactivation of virus in the intranasal environment is one possible approach. the work described here investigated the sensitivity of influenza viruses to low p ...200717509128
phenotypic properties resulting from directed gene segment reassortment between wild-type a/sydney/5/97 influenza virus and the live attenuated vaccine strain.widespread use of a live-attenuated influenza vaccine (laiv) in the united states (licensed as flumist) raises the possibility that vaccine viruses will contribute gene segments to the type a influenza virus gene pool. progeny viruses possessing new genotypes might arise from genetic reassortment between circulating wild-type (wt) and vaccine strains, but it will be difficult to predict whether they will be viable or exhibit novel properties. to begin addressing these uncertainties, reverse-gene ...200717599381
evaluation of replication and pathogenicity of avian influenza a h7 subtype viruses in a mouse model.avian influenza a h7 subtype viruses pose a significant threat to human health because of their ability to transmit directly from domestic poultry to humans and to cause disease and, sometimes, death. although it is important to develop vaccines against viruses of this subtype, very limited information is available on the immune response and pathogenesis of h7 viruses in animal models such as mice and ferrets. ten h7 viruses were selected for possible vaccine development on the basis of their ph ...200717634234
pathogenesis of avian influenza (h7) virus infection in mice and ferrets: enhanced virulence of eurasian h7n7 viruses isolated from humans.before 2003, only occasional case reports of human h7 influenza virus infections occurred as a result of direct animal-to-human transmission or laboratory accidents; most of these infections resulted in conjunctivitis. an increase in isolation of avian influenza a h7 viruses from poultry outbreaks and humans has raised concerns that additional zoonotic transmissions of influenza viruses from poultry to humans may occur. to better understand the pathogenesis of h7 viruses, we have investigated th ...200717686867
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
in vivo prophylactic activity of qr-435 against h3n2 influenza virus infection.prophylaxis against influenza infection can take several forms, none of which is totally effective at preventing the spread of the disease. qr-435, an all-natural compound of green-tea extract and other agents, has been developed to protect against a range of viral infections, including the influenza subtype h3n2.200717890936
identification of h2n3 influenza a viruses from swine in the united states.although viruses of each of the 16 influenza a ha subtypes are potential human pathogens, only viruses of the h1, h2, and h3 subtype are known to have been successfully established in humans. h2 influenza viruses have been absent from human circulation since 1968, and as such they pose a substantial human pandemic risk. in this report, we isolate and characterize genetically similar avian/swine virus reassortant h2n3 influenza a viruses isolated from diseased swine from two farms in the united s ...200718093945
cross-protection against lethal h5n1 challenge in ferrets with an adjuvanted pandemic influenza vaccine.unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (hpai) of the h5n1 subtype has resulted in hundreds of human infections with a high fatality rate. this has highlighted the urgent need for the development of h5n1 vaccines that can be produced rapidly and in sufficient quantities. potential pandemic inactivated vaccines will ideally induce substantial intra-subtypic cross-protection in humans to warrant the option of use, either prior to or just after th ...200818167560
influenza virus transmission: basic science and implications for the use of antiviral drugs during a pandemic.recent and ongoing zoonotic infections of humans with avian influenza viruses have highlighted the importance of transmission in the development of an influenza pandemic. despite the ability of h5n1 influenza viruses to grow to high titers and cause severe disease in human hosts, these viruses do not spread efficiently from human-to-human. the question of what viral, host and environmental factors are required to render an influenza virus transmissible has therefore become very topical. recent w ...200718220963
cloning, expression and immunoassay detection of ferret ifn-gamma.ferrets (mustela putorius furo) develop symptoms upon influenza infection that resemble those of humans, including sneezing, body temperature variation and weight loss. highly pathogenic strains of influenza a, such as h5n1, have the capacity to cause severe illness or death in ferrets. the use of ferrets as a model of influenza infection is currently limited by a lack of species-specific immunological reagents. interferon gamma (ifn-gamma) plays a key role in the development of innate and adapt ...200818262264
avian influenza in birds and mammals.the disease syndromes caused by avian influenza viruses are highly variable depending on the host species infected, its susceptibility and response to infection and the virulence of the infecting viral strain. although avian influenza viruses have a broad host range in general, it is rare for an individual strain or subtype to infect more than one species. the h5n1 highly pathogenic avian influenza virus (hpaiv) lineages of viruses that descended from a/goose/guandong/96 (h5n1 hpaiv) are unusual ...200918485480
plasmid dna-based vaccines protect mice and ferrets against lethal challenge with a/vietnam/1203/04 (h5n1) influenza virus.plasmid dna (pdna) vaccines represent an alternative to conventional inactivated influenza vaccines that are likely to experience supply constraints during a pandemic. several vaxfectin-formulated pdna vaccines were tested in mice and ferrets for efficacy against a lethal challenge with the highly pathogenic a/vietnam/1203/04 (h5n1) influenza virus strain; the vaccines encoded influenza a virus hemagglutinin (ha), and/or nucleoprotein (np), and m2 protein. complete protection from death and dise ...200818513153
heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus dna antigens.the persistent evolution of highly pathogenic avian influenza (hpai) highlights the need for novel vaccination techniques that can quickly and effectively respond to emerging viral threats. we evaluated the use of optimized consensus influenza antigens to provide broad protection against divergent strains of h5n1 influenza in three animal models of mice, ferrets, and non-human primates. we also evaluated the use of in vivo electroporation to deliver these vaccines to overcome the immunogenicity ...200818575608
a live attenuated cold-adapted influenza a h7n3 virus vaccine provides protection against homologous and heterologous h7 viruses in mice and ferrets.the appearance of human infections caused by avian influenza a h7 subtype viruses underscores their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. a live attenuated h7n3 virus vaccine was generated by reverse genetics using the ha and na genes of a low pathogenicity a/chicken/bc/cn-6/04 (h7n3) virus and the six internal protein genes of the cold-adapted a/ann arbor/6/60 ca (h2n2) virus. the reassortant h7n3 bc 04 ca vaccine virus was temperatu ...200818585748
treatment of influenza a (h1n1) virus infections in mice and ferrets with cyanovirin-n.cyanovirin-n (cv-n), a protein derived from nostoc ellipsosporum, neutralizes influenza virus infectivity by binding to specific high-mannose oligosaccharides (oligomannose-8 and -9) at glycosylation sites on the viral hemagglutinin ha1 subunit. mouse-adapted viruses lose sensitivity to cv-n due to ha1 mutations that eliminate these glycosylation sites. recently we created a hybrid (reassortant) influenza a/wsn/33 (h1n1) virus containing the ha gene of a/new caledonia/20/99 (h1n1) with an asp225 ...200818601954
domestic pigs have low susceptibility to h5n1 highly pathogenic avian influenza viruses.genetic reassortment of h5n1 highly pathogenic avian influenza viruses (hpai) with currently circulating human influenza a strains is one possibility that could lead to efficient human-to-human transmissibility. domestic pigs which are susceptible to infection with both human and avian influenza a viruses are one of the natural hosts where such reassortment events could occur. virological, histological and serological features of h5n1 virus infection in pigs were characterized in this study. two ...200818617994
animal models in influenza vaccine testing.the threat of a pandemic outbreak of influenza a h5n1 and h2n2 has brought attention to the development of new vaccines. regulatory authorities require companies to provide data proving the effectiveness of vaccines, which cannot, however, be based on real efficacy data in humans. a weight-of-evidence approach may be used, based on evidence of protection in an appropriate animal model and the satisfaction of the surrogate end points in the clinical situation. in this review, we will discuss vari ...200818665776
oseltamivir-resistant influenza a viruses are transmitted efficiently among guinea pigs by direct contact but not by aerosol.influenza viruses resistant to the neuraminidase (na) inhibitor oseltamivir arise under drug selection pressure both in vitro and in vivo. several mutations in the active site of the viral na are known to confer relative resistance to oseltamivir, and influenza viruses with certain oseltamivir resistance mutations have been shown to transmit efficiently among cocaged ferrets. however, it is not known whether na mutations alter aerosol transmission of drug-resistant influenza virus. here, we demo ...200818684820
gene expression analysis of host innate immune responses during lethal h5n1 infection in ferrets.how viral and host factors contribute to the severe pathogenicity of the h5n1 subtype of avian influenza virus infection in humans is poorly understood. we identified three clusters of differentially expressed innate immune response genes in lungs from h5n1 (a/vietnam/1203/04) influenza virus-infected ferrets by oligonucleotide microarray analysis. interferon response genes were more strongly expressed in h5n1-infected ferret lungs than in lungs from ferrets infected with the less pathogenic h3n ...200818684821
replication and transmission of h9n2 influenza viruses in ferrets: evaluation of pandemic potential.h9n2 avian influenza a viruses are endemic in poultry of many eurasian countries and have caused repeated human infections in asia since 1998. to evaluate the potential threat of h9n2 viruses to humans, we investigated the replication and transmission efficiency of h9n2 viruses in the ferret model. five wild-type (wt) h9n2 viruses, isolated from different avian species from 1988 through 2003, were tested in vivo and found to replicate in ferrets. however these viruses achieved mild peak viral ti ...200818698430
live, attenuated influenza virus (laiv) vehicles are strong inducers of immunity toward influenza b virus.historically, vaccines developed toward influenza viruses of the b type using methodologies developed for influenza a viruses as a blueprint have not been equally efficacious or effective. because most influenza research and public attention concerns influenza a viruses, these shortcomings have not been adequately addressed. in this manuscript, we utilized different influenza vaccine vehicles to compare immunogenicity and protection in mice and ferrets after vaccination against an influenza b vi ...200818708106
avian influenza h6 viruses productively infect and cause illness in mice and ferrets.influenza pandemic preparedness has focused on influenza virus h5 and h7 subtypes. however, it is not possible to predict with certainty which subtype of avian influenza virus will cause the next pandemic, and it is prudent to include other avian influenza virus subtypes in pandemic preparedness efforts. an h6 influenza virus was identified as a potential progenitor of the h5n1 viruses that emerged in hong kong in 1997. this virus continues to circulate in the bird population in asia, and other ...200818715930
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
plant-derived hemagglutinin protects ferrets against challenge infection with the a/indonesia/05/05 strain of avian influenza.the global spread of highly pathogenic avian influenza virus (h5n1 subtype) has promoted efforts to develop human vaccines against potential pandemic outbreaks. however, current platforms for influenza vaccine production are cumbersome, limited in scalability and often require the handling of live infectious virus. we describe the production of hemagglutinin from the a/indonesia/05/05 strain of h5n1 influenza virus by transient expression in plants, and demonstrate the immunogenicity and protect ...200919100806
viral rna polymerase complex promotes optimal growth of 1918 virus in the lower respiratory tract of ferrets.the 1918 influenza pandemic was the most devastating outbreak of infectious disease in human history, accounting for about 50 million deaths worldwide. in addition to a significant number of cases of secondary bacterial pneumonia, this highly pathogenic strain of influenza a virus caused fatal primary viral pneumonia. to identify the viral gene(s) chiefly responsible for the high virulence of the 1918 virus, we generated a series of reassortants between the 1918 virus and a contemporary human h1 ...200919114663
intranasal administration of alpha interferon reduces seasonal influenza a virus morbidity in ferrets.the type i interferon (ifn) response represents one of the first lines of defense against influenza virus infections. in this study, we assessed the protective potential of exogenous ifn-alpha against seasonal and highly pathogenic influenza viruses in ferrets. intranasal treatment with ifn-alpha several hours before infection with the h1n1 influenza a virus strain a/ussr/90/77 reduced viral titers in nasal washes at least 100-fold compared to mock-treated controls. ifn-treated animals developed ...200919193792
h5n1 vaccine-specific b cell responses in ferrets primed with live attenuated seasonal influenza vaccines.live attenuated influenza h5n1 vaccines have been produced and evaluated in mice and ferrets that were never exposed to influenza a virus infection (suguitan et al., plos medicine, e360:1541, 2006). however, the preexisting influenza heterosubtypic immunity on live attenuated h5n1 vaccine induced immune response has not been evaluated.200919209231
human ha and polymerase subunit pb2 proteins confer transmission of an avian influenza virus through the air.the influenza virus genes that confer efficient transmission of epidemic and pandemic strains in humans have not been identified. the rapid spread and severe disease caused by the 1918 influenza pandemic virus makes it an ideal virus to study the transmissibility of potentially pandemic influenza strains. here, we used a series of human 1918-avian h1n1 influenza reassortant viruses to identify the genetic determinants that govern airborne transmission of avian influenza viruses. we have demonstr ...200919211790
experimental infection of pigs with the human 1918 pandemic influenza virus.swine influenza was first recognized as a disease entity during the 1918 "spanish flu" pandemic. the aim of this work was to determine the virulence of a plasmid-derived human 1918 pandemic h1n1 influenza virus (reconstructed 1918, or 1918/rec, virus) in swine using a plasmid-derived a/swine/iowa/15/1930 h1n1 virus (1930/rec virus), representing the first isolated influenza virus, as a reference. four-week-old piglets were inoculated intratracheally with either the 1930/rec or the 1918/rec virus ...200919224986
the public health impact of avian influenza viruses.influenza viruses with novel hemagglutinin and 1 or more accompanying genes derived from avian influenza viruses sporadically emerge in humans and have the potential to result in a pandemic if the virus causes disease and spreads efficiently in a population that lacks immunity to the novel hemagglutinin. since 1997, multiple avian influenza virus subtypes have been transmitted directly from domestic poultry to humans and have caused a spectrum of human disease, from asymptomatic to severe and fa ...200919276438
isolation and genetic characterization of h5n2 influenza viruses from pigs in korea.due to dual susceptibility to both human and avian influenza a viruses, pigs are believed to be effective intermediate hosts for the spread and production of new viruses with pandemic potential. in early 2008, two swine h5n2 viruses were isolated from our routine swine surveillance in korea. the sequencing and phylogenetic analysis of surface proteins revealed that the sw/korea/c12/08 and sw/korea/c13/08 viruses were derived from avian influenza viruses of the eurasian lineage. however, although ...200919359528
development of a live-attenuated influenza b deltans1 intranasal vaccine candidate.we discovered a unique, single amino acid mutation in the influenza b m1 protein promoting viral growth of ns1 truncation mutants in vero cells. due to this mutation, we were able to generate an influenza b virus lacking the complete ns1 open reading frame (deltans1-b virus) by reverse genetics, which was growing to titers of 8log(10)tcid(50)/ml in a vero cell culture-based micro-carrier fermenter. the deltans1-b vaccine candidate was attenuated in ifn-competent hosts such as human alveolar epit ...200919366569
Displaying items 101 - 200 of 593