Publications

an elisa for detection of antibodies against influenza a nucleoprotein in humans and various animal species.	a double antibody sandwich blocking elisa, using a monoclonal antibody (mab) against influenza a nucleoprotein (np) was developed to detect antibodies against influenza. collections of serum samples were obtained from human and various animal species. all influenza a subtypes induced antibodies against hemagglutinins and np. a close correlation between titers of the hemagglutination inhibition (hi) test and the np-elisa was seen. antibodies against influenza np were demonstrated in serum samples ...	1990	2174233
molecular characterization of a new hemagglutinin, subtype h14, of influenza a virus.	two influenza a viruses whose hemagglutinin (ha) did not react with any of the reference antisera for the 13 recognized ha subtypes were isolated from mallard ducks in the ussr. antigenic analysis by hemagglutination inhibition and double immunodiffusion tests showed that the has of these viruses are similar to each other but distinct from the has of other influenza a viruses. nucleotide sequence analysis showed that these ha genes differ from each other by only 21 nucleotides. however, they dif ...	1990	2238469
kinins are generated in nasal secretions during influenza a infections in ferrets.	infection of ferrets with influenza a virus results in a disease syndrome that is similar to that observed in humans. to examine the pathophysiology of this disease, ferrets were challenged with either h1n1 influenza virus or placebo. sign scores and rectal temperatures were recorded periodically during the 9 days after infection. nasal lavages were also collected during this time period and the content of kinins, histamine, cells, and total protein in these lavages was assessed. in infected ani ...	1990	2368965
virulence of rimantadine-resistant human influenza a (h3n2) viruses in ferrets.	the influence of rimantadine-resistance mutations on the virulence of human h3n2 viruses in ferrets was examined. the similarities in virulence of the drug-resistant mutants with single amino acid substitutions at three different locations, 27, 30, and 31, within the m2 sequence and their corresponding sensitive wild-type isolates contrasted with differences in virulence between the three pairs of viruses. these data provide further evidence that rimantadine-resistant viruses that emerge during ...	1991	1940477
dominant-negative mutants as antiviral agents: simultaneous infection with the cold-adapted live-virus vaccine for influenza a protects ferrets from disease produced by wild-type influenza a.	the attenuated cold-adapted strain of influenza a virus that is a candidate live-virus vaccine suppressed clinical disease in ferrets when given simultaneously with a virulent epidemic strain of influenza a virus. the cold-adapted virus effectively prevented disease, even when the epidemic strain was of a different subtype than the attenuated virus. in this case, ferrets given a mixed inoculum produced antibody to both subtypes in the absence of clinical disease, indicating that both viruses are ...	1991	1955719
attachment of influenza a virus to ferret tracheal epithelium at different maturational stages.	influenza virus attaches primarily to ciliated cells in mature airways epithelium. this process is mediated by a viral envelope glycoprotein (hemagglutinin) that binds to sialic acid-containing receptors in the apical membrane of host cells. the purpose of this study was to determine the cellular distribution of these receptors as a function of tracheal epithelial maturation in the ferret, which is susceptible to influenza virus infection at all ages and undergoes postnatal ciliation. to assay f ...	1991	1986780
characterization of a new avian-like influenza a virus from horses in china.	in march 1989 a severe outbreak of respiratory disease occurred in horses in the jilin and heilongjiang provinces of northeast china that caused up to 20% mortality in some herds. an influenza virus of the h3n8 subtype was isolated from the infected animals and was antigenically and molecularly distinguishable from the equine 2 (h3n8) viruses currently circulating in the world. the reference strain a/equine/jilin/1/89 (h3n8) was most closely related to avian h3n8 influenza viruses. sequence comp ...	1992	1314452
the attenuation phenotype conferred by the m gene of the influenza a/ann arbor/6/60 cold-adapted virus (h2n2) on the a/korea/82 (h3n2) reassortant virus results from a gene constellation effect.	a single gene reassortant (sgr) virus that derived its m gene from the attenuated influenza a/ann arbor/6/60 cold-adapted (ca) donor virus and the remaining genes from the a/korea/82 (h3n2) wild type (wt) virus (designated a/korea/82 ca m-sgr) was previously shown to be attenuated in mice, hamsters, ferrets, and humans. the attenuation (att) phenotype of this sgr virus could result directly from an altered function of the mutant m gene product of the a/ann arbor/6/60 ca virus, which differs from ...	1992	1413993
influenza vaccine strain selection: equivalence of two antigenically distinct haemagglutinin variants of 1989 h3n2 influenza a virus in protection of mice.	precise antigenic analysis with haemagglutinin-inhibition (hi) tests of 1989 h3n2 influenza a viruses with polyclonal ferret, rabbit and mouse antisera has shown, first, significant differences among 1989 wild-type isolates, second, antigenic differences between two high-yield vaccine candidate reassortant viruses, third, significant antigenic differences of one reassortant (x-105) from the wild-type virus (a/guangdong a/39) from which it was derived, and fourth, dependence of antigenic characte ...	1992	1502837
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 ...	1993	8212831
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 ...	1993	8246828
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 ...	1993	8356790
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 ...	1993	8423445
potentiation of infectivity and pathogenesis of influenza a virus by a house dust mite protease.	common house dust mites (e.g., dermatophagoides farinae) excrete a serine-type (df) protease. df protease obtained from cultured mites enhanced viral replication in vitro via proteolytic cleavage of viral hemagglutinin (ha) into ha1 and ha2, which confers potent viral infectivity. its potency is 2- to 5-fold higher than bovine trypsin or human plasmin. df protease also markedly accelerated virus propagation in vivo: a minute quantity of protease (estimated delivered amount, 0.8-3.2 micrograms) p ...	1994	7930699
efficacy of 2'-deoxy-2'-fluororibosides against influenza a and b viruses in ferrets.	single-dose treatments (5 to 40 mg/kg of body weight given intraperitoneally) of ferrets with 2'-deoxy-2'-fluoroguanosine or its prodrug, 2,6-diamino-purine-2'-fluororiboside, 1 h after infection with influenza a virus significantly inhibited replication of virus in the upper respiratory tract, resulting in amelioration of fever and nasal inflammation. replication of virus in the lower respiratory tract was also reduced > 100-fold, but three doses were required to prevent replication in the lung ...	1994	7986023
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 ...	1994	8138990
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 ...	1994	8147099
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 ...	1994	8195389
[influenza in the 1994/95 season; composition of vaccine for the 1995/96 season].	the 1994/'95 season in the netherlands was marked by a limited influenza activity which only emerged in late february. the influenza activity remained elevated until the end of april, which is unusually late, and epidemic activity was only reported in the south of the country. both influenza a/h3n2 and b viruses were isolated in this period. in addition, influenza a/hini viruses were isolated for the first time since march 1993, from two patients. the majority of the influenza a strains that cir ...	1995	7477582
4-guanidino-neu5ac2en fails to protect chickens from infection with highly pathogenic avian influenza virus.	the effectiveness of the novel sialidase inhibitor 4-guanidino-neu5ac2en, which is highly effective in mouse and ferret models of influenza virus infection (von itzstein et al. (1993) nature 363, 418-423), has been assessed as a prophylactic agent in the prevention of infection of chickens with highly pathogenic avian influenza viruses. at best a small delay in the onset of pyrexia and death was observed with one strain of fowl plague virus, but not with two other strains. these results demonstr ...	1995	7486955
otologic and systemic manifestations of experimental influenza a virus infection in the ferret.	in an effort to further validate an animal model and to better define the mechanisms relating viral upper respiratory tract infections and acute otitis media, we infected 10 ferrets intranasally with influenza a virus. infection was monitored by cultures and antibody titers, illness was monitored by signs and temperatures, and otologic complications were monitored by otoscopy, tympanometry, and eustachian tube function testing. all animals became infected. forced-response test results showed pro ...	1995	7700664
pathogenicity of influenza a/seal/mass/1/80 virus mutants for mammalian species.	increases in infectiousness, neurotropism and virulence were found in a laboratory variant of influenza a/seal/massachussets/1/80 (h7n7) virus having a highly cleavable hemagglutinin. sequential passage from host to host further increased pathogenicity of the h7n7 virus in mice, ferrets and rats.	1995	7710359
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 ...	1995	8578828
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.	1995	8585752
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 ...	1996	9029775
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 ...	1997	9060631
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 ...	1997	9375016
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 ...	1998	9517945
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 ...	1998	9517946
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 ...	1998	9585868
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 ...	1999	10191214
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 ...	1999	10543741
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 ...	1999	10595865
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 ...	2000	10602727
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 ...	2000	10708809
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 ...	2000	10745239
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 ...	2000	10799787
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 ...	2000	11228888
development and characterization of lyophilized dna vaccine formulations.	the potential applications of using plasmid dna for immunization and other gene therapy approaches have been discussed in an increasing number of publications in the past few years. injection of mouse muscle with naked dna (plasmid dna in saline) resulted in significant episomal expression from a number of encoded reporter genes such as firefly luciferase, chloramphenicol acetyltransferase, and β-galactosidase (1). dna vaccination has been shown to induce neutralizing antibodies against the gene ...	2000	21374306
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 ...	2001	11530187
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 ...	2002	11932409
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 ...	2002	11972972
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 ...	2002	12036429
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 ...	2002	12062393
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 ...	2002	12103431
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 ...	2002	12355356
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 ...	2003	12445939
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 ...	2003	12601764
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 ...	2003	14575126
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 ...	2003	14575129
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 ...	2003	14593594
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 ...	2004	14694130
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 ...	2004	14963236
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 ...	2004	15163508
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 ...	2004	15297047
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 ...	2004	15351492
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 ...	2004	15478068
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 ...	2004	15496238
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 ...	2005	15585193
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 ...	2005	15681421
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 = ...	2005	15767421
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 ...	2005	15780741
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 ...	2005	15795074
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 ...	2005	16014953
[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 ...	2005	16308530
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 ...	2006	16459194
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 ...	2006	16460844
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 ...	2006	16556800
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 ...	2006	16569867
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 ...	2006	16573202
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 ...	2006	16621180
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 ...	2006	16622191
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. ...	2006	16880383
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.	2006	16968127
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 ...	2006	16991078
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 ...	2007	17250978
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 ...	2007	17403562
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 ...	2007	17412461
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 ...	2007	17459930
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 ...	2007	17509128
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 ...	2007	17599381
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 ...	2007	17634234
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 ...	2007	17686867
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 ...	2007	17717141
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.	2007	17890936
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 ...	2007	18093945
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 ...	2007	18220963
generation of candidate human influenza vaccine strains in cell culture - rehearsing the european response to an h7n1 pandemic threat.	although h5n1 avian influenza viruses pose the most obvious imminent pandemic threat, there have been several recent zoonotic incidents involving transmission of h7 viruses to humans. vaccines are the primary public health defense against pandemics, but reliance on embryonated chickens eggs to propagate vaccine and logistic problems posed by the use of new technology may slow our ability to respond rapidly in a pandemic situation.	2007	19432631
chloroquine is effective against influenza a virus in vitro but not in vivo.	chloroquine is an inexpensive and widely available 9-aminoquinolone used in the management of malaria. recently, in vitro assays suggest that chloroquine may have utility in the treatment of several viral infections including influenza.	2007	19453426
a plant-produced influenza subunit vaccine protects ferrets against virus challenge.	influenza a viruses are of major concern for public health, causing worldwide epidemics associated with high morbidity and mortality. vaccines are critical for protection against influenza, but given the recent emergence of new strains with pandemic potential, and some limitations of the current production systems, there is a need for new approaches for vaccine development.	2008	19453491
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 ...	2008	18262264
the pig as a mixing vessel for influenza viruses: human and veterinary implications.	influenza a viruses are highly infectious respiratory pathogens that can infect many species. birds are the reservoir for all known influenza a subtypes; and novel influenza viruses can emerge from birds and infect mammalian species including humans. because swine are susceptible to infection with both avian and human influenza viruses, novel reassortant influenza viruses can be generated in this mammalian species by reassortment of influenza viral segments leading to the "mixing vessel" theory. ...	2008	19565018
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 ...	2008	18513153
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 ...	2008	18575608
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 ...	2008	18585748
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 ...	2008	18601954
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 ...	2008	18617994
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 ...	2008	18665776
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 ...	2008	18684820
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 ...	2008	18684821