protection against virulent h5 avian influenza virus infection in chickens by an inactivated vaccine produced with recombinant vaccinia virus.a cloned cdna copy of the haemagglutinin (ha) gene of a/chicken/scotland/59 (h5n1) influenza virus has been expressed in vaccinia virus. this pox virus is poorly infectious or non-infectious for chickens. however, immunization of chickens with lysates of cell cultures infected with the recombinant vaccinia virus, that had been emulsified with adjuvant and which contained an estimated 0.5 microgram influenza ha, elicited a substantial neutralizing antibody response to influenza virus. challenges ...19883048009
complete sequence of a cdna clone of the hemagglutinin gene of influenza a/chicken/scotland/59 (h5n1) virus: comparison with contemporary north american and european strains. 19883375087
host range of a/chicken/pennsylvania/83 (h5n2) influenza virus.the highly pathogenic a/chicken/penn./1370/83 (h5n2) avian influenza virus, which caused 80% mortality in chickens in pennsylvania, produced only mild transient illness in experimentally infected pheasants, little or no clinical signs in ring-billed gulls and pigs, and no clinical signs in pekin ducks. virus could be recovered from only the upper respiratory tract of gulls and pigs for 1-2 days. infection in ducks resulted in intestinal replication of virus in only 1 out of 12 ducks. by contrast ...19853985875
deduced amino acid sequences of the haemagglutinin of h5n1 avian influenza virus isolates from an outbreak in turkeys in norfolk, england.the deduced amino acid sequences of the haemagglutinins of avian influenza viruses, isolated from an outbreak in turkeys in norfolk, england in 1991/92, were determined by pcr amplification and cycle sequencing. both the highly pathogenic and avirulent isolates had the same cleavage site sequence with multiple-basic amino acids, which normally would be expected only for the former. clones derived by plaque picking from the highly pathogenic isolate ranged from low to very high pathogenicity in v ...19947506519
effect of an h5n1 avian influenza virus infection on the immune system of mallard ducks.avian influenza virus (aiv) of waterfowl origin, a/mallard/ohio/184/86 (h5n1), was used to evaluate the effect of aiv infection on the functional capabilities of the immune system in mallard ducks. the three main arms of the immune system--humoral, cell-mediated, and cellular--were evaluated. the integrity of the humoral immune system after aiv infection was evaluated by measuring total immunoglobulin and igg antibody production to sheep erythrocytes and brucella abortus antigen using hemaggluti ...19938257381
effect of intravenous inoculation of avian influenza virus on reproduction and growth in mallard avian influenza virus isolate, a/mallard/ohio/184/86 (h5n1), was evaluated for its effects on reproduction in isolation-reared adult mallard ducks (anas platyrhynchos) and growth rate in juvenile mallards after intravenous inoculation. there was a significant decrease in egg production in the experimental group during the first week after inoculation, but it returned to the normal production level during the second week. no effect was seen on egg weight, shape, or fertility. ducklings receivi ...19938258848
deduced amino acid sequences at the haemagglutinin cleavage site of avian influenza a viruses of h5 and h7 subtypes.the amino acid sequences at the haemagglutinin cleavage sites of 9 avian influenza a viruses of h5 subtype (5 high and 4 low pathogenicity for chickens) and 21 of h7 subtype (13 high and 8 low pathogenicity for chickens) were determined by direct rna sequencing, pcr amplification sequencing or both. none of the viruses of low pathogenicity had multiple basic amino acids at the cleavage site. all highly pathogenic viruses had an insert of basic amino acids at the cleavage site, except a/chicken/s ...19938503786
cleavability of hemagglutinin from an extremely virulent strain of avian influenza virus containing a unique cleavage site avian influenza virus, a/turkey/england/50-92/91 (h5n1), showed extremely high virulence in chickens, although its hemagglutinin (ha) cleavage site sequence (r-k-r-k-t-r), having a nonbasic (thr) residue at the second position (p-2) from the carboxyl terminus of ha1, does not conform to the previously established consensus sequence motif, x-x-r/k-x-r/k-r (x = nonbasic residue), for highly virulent phenotype of the h5 virus. when we evaluated the ha cleavability of this strain in chicken embry ...19958593304
neuropathological studies of chickens infected with highly pathogenic avian influenza viruses.central nervous system lesions of chickens inoculated with three highly pathogenic avian influenza virus strains, a/chicken/victoria/1/85 (h7n7), a/turkey/england/50-92/91 (h5n1), and a/tern/south africa/61 (h5n3), were examined histologically and immunohistochemically. the chickens either died within 7 days of inoculation or were killed 2 weeks after inoculation. no significant differences were observed in the lesions induced by these three viruses. the lesions were divided into two types, diss ...19968920214
isolation of avian influenza a(h5n1) viruses from humans--hong kong, may-december 1997.a strain of influenza virus that previously was known to infect only birds has been associated with infection and illness in humans in hong kong. the first known human case of influenza type a(h5n1) occurred in a 3-year-old child who died from respiratory failure in may 1997. in hong kong, the virus initially was identified as influenza type a, but the subtype could not be determined using standard reagents. by august, cdc; the national influenza center, rotterdam, the netherlands; and the natio ...19979414153
characterization of an avian influenza a (h5n1) virus isolated from a child with a fatal respiratory avian h5n1 influenza a virus (a/hong kong/156/97) was isolated from a tracheal aspirate obtained from a 3-year-old child in hong kong with a fatal illness consistent with influenza. serologic analysis indicated the presence of an h5 hemagglutinin. all eight rna segments were derived from an avian influenza a virus. the hemagglutinin contained multiple basic amino acids adjacent to the cleavage site, a feature characteristic of highly pathogenic avian influenza a viruses. the virus caused 87.5 ...19989430591
update: isolation of avian influenza a(h5n1) viruses from humans--hong kong, of january 6, 1998, a total of 16 confirmed and three suspected cases of human infection with avian influenza a(h5n1) viruses have been identified in hong kong. confirmed cases are those from which an influenza a(h5n1) virus was isolated or in which a seroconversion to influenza a(h5n1) virus was detected by a neutralization assay. suspected cases are those with influenza-like illness (ili) and preliminary laboratory evidence of influenza a(h5n1) infection. this report summarizes interim find ...19989436713
influenza a virus subtype h5n1 infection in humans. 19979447788
from the centers for disease control and prevention. isolation of avian influenza a(h5n1) viruses from humans--hong kong, may-december 1997. 19989450697
influenza a virus subtype h5n1 infection in humans: update. 19979458573
from the centers for disease control and prevention. update: isolation of avian influenza a(h5n1) viruses from humans--hong kong, 1997-1998. 19989459456
influenza a virus subtype h5n1 infection in hong kong--update. 19989476418
clinical features and rapid viral diagnosis of human disease associated with avian influenza a h5n1 virus.human infection with an avian influenza a virus (subtype h5n1) was reported recently in hong kong. we describe the clinical presentation of the first 12 patients and options for rapid viral diagnosis.19989482437
human influenza a h5n1 virus related to a highly pathogenic avian influenza may, 1997, a 3-year-old boy in hong kong was admitted to the hospital and subsequently died from influenza pneumonia, acute respiratory distress syndrome, reye's syndrome, multiorgan failure, and disseminated intravascular coagulation. an influenza a h5n1 virus was isolated from a tracheal aspirate of the boy. preceding this incident, avian influenza outbreaks of high mortality were reported from three chicken farms in hong kong, and the virus involved was also found to be of the h5 subtype.19989482438
update: isolation of avian influenza a(h5n1) viruses from human beings--hong kong, 1997-1998. 19989581152
[influenza a(h5n1): current status]. 19989599174
[influenza a(h5n1) in hong kong: forerunner of a pandemic or an only scientifically interesting phenomenon and a useful exercise in pandemiology?].from a three-year old boy in hong kong who died in may 1997 with an extensive influenza pneumonia an influenza a virus has been isolated which was, first at the national influenza centre of the netherlands, identified as belonging to subtype h5n1. presumably the patient had acquired the infection directly from an outbreak of fowl plague among chickens. as far as is known this is the first case of the isolation of an influenza virus belonging to one of the subtypes h4-h15 from a human influenza p ...19989602508
comparisons of highly virulent h5n1 influenza a viruses isolated from humans and chickens from hong kong.genes of an influenza a (h5n1) virus from a human in hong kong isolated in may 1997 were sequenced and found to be all avian-like (k. subbarao et al., science 279:393-395, 1998). gene sequences of this human isolate were compared to those of a highly pathogenic chicken h5n1 influenza virus isolated from hong kong in april 1997. sequence comparisons of all eight rna segments from the two viruses show greater than 99% sequence identity between them. however, neither isolate's gene sequence was clo ...19989658115
human influenza virus a/hongkong/156/97 (h5n1) infection.introduction of influenza viruses with gene segments of avian origin into the human population may result in the emergence of new pathogenic human influenza viruses. the recent infection of a 3-year-old boy with an influenza a (h5n1) virus of avian origin can be considered as an example of such an event. however, this virus, influenza a/hong kong/156/97 (h5n1) and the 17 additional h5n1 viruses isolated from humans by the end of 1997 lack the ability to spread efficiently amongst humans and ther ...19989682346
[influenza remains an unpredictable infection].influenza virus a (h5n1) was isolated from the tracheal swab of a 3-year-old boy who died from influenza with the raye syndrome in hong kong in may, 1997. up to the present time, influenza viruses with hemagglutinin h5 were known to circulate only among birds. they caused a variety of diseases: from asymptomatic to epizootic with 100% mortality, particularly among chickens. the main difference between virulent and avirulent strains is as follows: virulent viruses are isolated from all tissues of ...19989702816
influenza a(h5n1). 19989707895
laboratory containment for influenza a h5n1 virus: level 2, level 3, or level 3+?the recent alert over bird flu (influenza a h5n1) in hong kong has ruffled feathers in some countries, including the united kingdom, as to how the virus should be handled in clinical and research laboratories.19989718852
[influenza a (h5n1) in hong kong: forerunner of a pandemic or just a scientifically interesting phenomenon and a useful exercise in pandemiology?].in 1997, 18 influenza patients were detected who were infected with influenza a(h5n1) virus. six patients died. presumably most of the patients had acquired the infection directly from chickens with the fowl plague prevalent in china in 1997. these are the first reported cases of isolation of influenza viruses belonging to one of the h4-h15 subtypes from human influenza patients. man-to-man transmission of the virus has not been demonstrated but cannot be excluded in every case. genetic analyses ...19989749297
[evaluation of a rapid enzyme immunoassay membrane test for diagnosis of influenza a virus infection].a rapid enzyme immunoassay membrane test, directigen flu a (becton dickinson, usa), was evaluated by using virus isolates and clinical specimens. the reference laboratory diagnosis was based on the results of virus isolation. directigen flu a was reactive for all subtypes of human influenza a viruses, including reference strains of h1n1, h2n2 and h3n2. moreover, h5n1 (hongkong/156/97) was also detected by this kit. no cross reactivity was detected with other respiratory viruses. directigen flu a ...19989780586
characterization of influenza a/hongkong/156/97 (h5n1) virus in a mouse model and protective effect of zanamivir on h5n1 infection in mice.a recent outbreak of influenza in hong kong was caused by a highly virulent virus of avian origin. concern that the appearance of such a virus in the human population may be a harbinger of a new pandemic has brought increased attention to the issue of antivirals available for treatment of influenza. a/hongkong/156/97 (h5n1), the first virus of h5n1 subtype isolated from a human host, is highly virulent in the mouse model and can infect mouse lungs without requiring adaptation. high mortality and ...19989815209
mink lung epithelial cells: unique cell line that supports influenza a and b virus replication.we have demonstrated for the first time that a mink lung epithelial cell line (mv1lu) supports the replication of influenza a and b viruses, including the recently isolated h5n1 avian and human hong kong strains, to titers comparable to those in mdck cells. these results suggest that mv1lu cells might serve as an alternative system for the isolation and cultivation of influenza a and b viruses and may be useful for vaccine development.19989817906
evaluation of antibody responses of emus (dromaius novaehollandiae) to avian influenza virus infection.emu antibody responses to avian influenza virus (aiv) infection were evaluated by the competitive enzyme-linked immunosorbent assay (c-elisa), agar gel immunodiffusion (agid) and hemagglutination inhibition (hi) tests. all birds infected with aiv h5n1, h5n3, or h7n7 developed antinucleoprotein (np) antibodies as early as 7 days postinfection as detected by the c-elisa. the responses lasted 49 days for the emus receiving h5n3 and at least 56 days for emus receiving the other two viruses. by evalu ...19989876845
characterization of avian h5n1 influenza viruses from poultry in hong kong.the transmission of avian h5n1 influenza viruses to 18 humans in hong kong in 1997 with six deaths established that avian influenza viruses can transmit to and cause lethal infection in humans. this report characterizes the antigenic and biological properties of the h5n1 influenza viruses isolated from chickens, ducks, and geese from farms and poultry markets in hong kong during 1997 and compares them with those of virus isolated from the index human case. each of the h5n1 viruses from hong kong ...19989878612
the surface glycoproteins of h5 influenza viruses isolated from humans, chickens, and wild aquatic birds have distinguishable 1997, 18 confirmed cases of human influenza arising from multiple independent transmissions of h5n1 viruses from infected chickens were reported from hong kong. to identify possible phenotypic changes in the hemagglutinin (ha) and neuraminidase (na) of the h5 viruses during interspecies transfer, we compared the receptor-binding properties and na activities of the human and chicken h5n1 isolates from hong kong and of h5n3 and h5n1 viruses from wild aquatic birds. all h5n1 viruses, including t ...19999882316
protection against a lethal avian influenza a virus in a mammalian system.the question of how best to protect the human population against a potential influenza pandemic has been raised by the recent outbreak caused by an avian h5n1 virus in hong kong. the likely strategy would be to vaccinate with a less virulent, laboratory-adapted h5n1 strain isolated previously from birds. little attention has been given, however, to dissecting the consequences of sequential exposure to serologically related influenza a viruses using contemporary immunology techniques. such experi ...19999882351
characterization of the surface proteins of influenza a (h5n1) viruses isolated from humans in 1997-1998.influenza a (h5n1) viruses infected humans in hong kong between may and december, 1997. sixteen viruses, including 6 from fatal cases, were isolated during this outbreak. molecular analysis of the surface proteins genes encoding the hemagglutinin (ha) and neuraminidase (na) of these h5n1 isolates, of a subtype not previously known to infect humans, are presented. the 16 human h5 ha sequences contain multiple basic amino acids adjacent to the cleavage site, a motif associated with highly pathogen ...19999927579
dna vaccine encoding hemagglutinin provides protective immunity against h5n1 influenza virus infection in hong kong in 1997, a highly lethal h5n1 avian influenza virus was apparently transmitted directly from chickens to humans with no intermediate mammalian host and caused 18 confirmed infections and six deaths. strategies must be developed to deal with this virus if it should reappear, and prospective vaccines must be developed to anticipate a future pandemic. we have determined that unadapted h5n1 viruses are pathogenic in mice, which provides a well-defined mammalian system for immunological ...19999971791
biological heterogeneity, including systemic replication in mice, of h5n1 influenza a virus isolates from humans in hong h5n1 avian influenza a virus was transmitted to humans in hong kong in 1997. although the virus causes systemic infection and is highly lethal in chickens because of the susceptibility of the hemagglutinin to furin and pc6 proteases, it is not known whether it also causes systemic infection in humans. the clinical outcomes of infection in hong kong residents ranged widely, from mild respiratory disease to multiple organ failure leading to death. therefore, to understand the pathogenesis of in ...199910074171
rapid evolution of h5n1 influenza viruses in chickens in hong kong.the h5n1 avian influenza virus that killed 6 of 18 persons infected in hong kong in 1997 was transmitted directly from poultry to humans. viral isolates from this outbreak may provide molecular clues to zoonotic transfer. here we demonstrate that the h5n1 viruses circulating in poultry comprised two distinguishable phylogenetic lineages in all genes that were in very rapid evolution. when introduced into new hosts, influenza viruses usually undergo rapid alteration of their surface glycoproteins ...199910074191
detection of antibody to avian influenza a (h5n1) virus in human serum by using a combination of serologic assays.from may to december 1997, 18 cases of mild to severe respiratory illness caused by avian influenza a (h5n1) viruses were identified in hong kong. the emergence of an avian virus in the human population prompted an epidemiological investigation to determine the extent of human-to-human transmission of the virus and risk factors associated with infection. the hemagglutination inhibition (hi) assay, the standard method for serologic detection of influenza virus infection in humans, has been shown ...199910074505
[role of antineuraminidase antibodies in protection against influenza].for improving the anti-influenza vaccination efficacy, the choice of strains carrying up dated neuraminidase antigen (na) and the introduction of the optimal amount of na antigen in the vaccine are critical. monoclonal antibodies prepared against the neuraminidase n2 of a/beijing/32/92 showed na inhibition (ni) and neutralized (nt) the cells infection by influenza virus either at an early stage (group 2 antibodies inhibit virus binding to cells) or at a late stage of infection (group 1 antibodie ...199810188318
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
iscom vaccine induced protection against a lethal challenge with a human h5n1 influenza virus.recently avian influenza a viruses of the h5n1 subtype were shown to infect humans in the hong kong area, resulting in the death of six people. although these viruses did not efficiently spread amongst humans, these events illustrated that influenza viruses of subtypes not previously detected in humans could be at the basis of a new pandemic. in the light of this pandemic threat we evaluated and compared the efficacy of a classical non-adjuvanted subunit vaccine and a vaccine based on immune sti ...199910195770
upper respiratory tract reviewing recent advances in upper respiratory tract infections, we focus on five key topics. first, the use of ribavirin in the treatment of respiratory syncytial virus infection has been limited to the immunosuppressed. prophylaxis in high-risk patients with specific immunoglobulin is effective and a new monoclonal antibody shows promise. second, the efficacy of neuraminidase inhibitors in the treatment of influenza has become established. there are unresolved concerns about early implement ...199910228740
human cd8+ and cd4+ t lymphocyte memory to influenza a viruses of swine and avian species.recently, an avian influenza a virus (a/hong kong/156/97, h5n1) was isolated from a young child who had a fatal influenza illness. all eight rna segments were of avian origin. the h5 hemagglutinin is not recognized by neutralizing abs present in humans as a result of infection with the human h1, h2, or h3 subtypes of influenza a viruses. subsequently, five other deaths and several more human infections in hong kong were associated with this avian-derived virus. we investigated whether influenza ...199910358215
a mouse model for the evaluation of pathogenesis and immunity to influenza a (h5n1) viruses isolated from humans.during 1997 in hong kong, 18 human cases of respiratory illness, including 6 fatalities, were caused by highly pathogenic avian influenza a (h5n1) viruses. since h5 viruses had previously been isolated only from avian species, the outbreak raised questions about the ability of these viruses to cause severe disease and death in humans. to better understand the pathogenesis and immunity to these viruses, we have used the balb/c mouse model. four h5n1 viruses replicated equally well in the lungs of ...199910364342
the first case of h5n1 avian influenza infection in a human with complications of adult respiratory distress syndrome and reye's syndrome.avian influenza virus was not known to cause systemic infection in humans before. we report a 3-year-old boy with good past health who developed pneumonia caused by h5n1 avian influenza a virus (a/hong kong/156/97). the virus was isolated from a tracheal aspirate. there were complications of reye's syndrome, adult respiratory distress syndrome, and multiple organ system failure. he had a history of receiving aspirin. his adult respiratory distress syndrome did not respond to endotracheal surfact ...199910365363
case-control study of risk factors for avian influenza a (h5n1) disease, hong kong, may 1997, a 3-year-old boy in hong kong died of a respiratory illness related to influenza a (h5n1) virus infection, the first known human case of disease from this virus. an additional 17 cases followed in november and december. a case-control study of 15 of these patients hospitalized for influenza a (h5n1) disease was conducted using controls matched by age, sex, and neighborhood to determine risk factors for disease. exposure to live poultry (by visiting either a retail poultry stall or a ...199910395870
molecular characterization of h9n2 influenza viruses: were they the donors of the "internal" genes of h5n1 viruses in hong kong?the origin of the h5n1 influenza viruses that killed six of eighteen infected humans in 1997 and were highly pathogenic in chickens has not been resolved. these h5n1 viruses transmitted directly to humans from infected poultry. in the poultry markets in hong kong, both h5n1 and h9n2 influenza viruses were cocirculating, raising the possibility of genetic reassortment. here we analyze the antigenic and genetic features of h9n2 influenza viruses with different epidemiological backgrounds. the resu ...199910430948
poultry and the influenza h5n1 outbreak in hong kong, 1997: abridged chronology and virus isolation. 199910471177
mutation of neuraminidase cysteine residues yields temperature-sensitive influenza viruses.the influenza virus neuraminidase (na) is a tetrameric, virus surface glycoprotein possessing receptor-destroying activity. this enzyme facilitates viral release and is a target of anti-influenza virus drugs. the na structure has been extensively studied, and the locations of disulfide bonds within the na monomers have been identified. because mutation of cysteine residues in other systems has resulted in temperature-sensitive (ts) proteins, we asked whether mutation of cysteine residues in the ...199910482558
avirulent avian influenza virus as a vaccine strain against a potential human the influenza h5n1 virus incident in hong kong in 1997, viruses that are closely related to h5n1 viruses initially isolated in a severe outbreak of avian influenza in chickens were isolated from humans, signaling the possibility of an incipient pandemic. however, it was not possible to prepare a vaccine against the virus in the conventional embryonated egg system because of the lethality of the virus for chicken embryos and the high level of biosafety therefore required for vaccine production ...199910482580
genetic characterization of the pathogenic influenza a/goose/guangdong/1/96 (h5n1) virus: similarity of its hemagglutinin gene to those of h5n1 viruses from the 1997 outbreaks in hong kong.analysis of the sequences of all eight rna segments of the influenza a/g oose/guangdong/1/96 (h5n1) virus, isolated from a sick goose during an outbreak in guangdong province, china, in 1996, revealed that the hemagglutinin (ha) gene of the virus was genetically similar to those of the h5n1 viruses isolated in hong kong in 1997. however, the remaining genes showed greater similarity to other avian influenza viruses. notably, the neuraminidase gene did no have the 19-amino-acid deletion in the st ...199910484749
antibody response in individuals infected with avian influenza a (h5n1) viruses and detection of anti-h5 antibody among household and social contacts.the first documented outbreak of human respiratory disease caused by avian influenza a (h5n1) viruses occurred in hong kong in 1997. the kinetics of the antibody response to the avian virus in h5n1-infected persons was similar to that of a primary response to human influenza a viruses; serum neutralizing antibody was detected, in general, >/=14 days after symptom onset. cohort studies were conducted to assess the risk of human-to-human transmission of the virus. by use of a combination of serolo ...199910558929
risk of influenza a (h5n1) infection among health care workers exposed to patients with influenza a (h5n1), hong kong.the first outbreak of avian influenza a (h5n1) occurred among humans in hong kong in 1997. to estimate the risk of person-to-person transmission, a retrospective cohort study was conducted to compare the prevalence of h5n1 antibody among health care workers (hcws) exposed to h5n1 case-patients with the prevalence among nonexposed hcws. information on h5n1 case-patient and poultry exposures and blood samples for h5n1-specific antibody testing were collected. eight (3.7%) of 217 exposed and 2 (0.7 ...200010608786
isolation of avian influenza viruses in central oklahoma.aquatic birds are the natural hosts for influenza virus. it is established that avian influenza viruses provide the gene pool for the generation of new strains of human influenza virus, which can cause pandemic infections. the recent outbreak of an avian influenza virus (h5n1) in hong kong not only produced high mortality in chickens, but also resulted in six human fatalities. this outbreak indicates that avian influenza virus can be pathogenic for humans. we surveyed local waterfowl habitats by ...199910616258
distinct pathogenesis of hong kong-origin h5n1 viruses in mice compared to that of other highly pathogenic h5 avian influenza 1997, an outbreak of virulent h5n1 avian influenza virus occurred in poultry in hong kong (hk) and was linked to a direct transmission to humans. the factors associated with transmission of avian influenza virus to mammals are not fully understood, and the potential risk of other highly virulent avian influenza a viruses infecting and causing disease in mammals is not known. in this study, two avian and one human hk-origin h5n1 virus along with four additional highly pathogenic h5 avian influ ...200010627555
recent progress in anti-influenza chemotherapy.influenza virus infections in high risk individuals, such as infants, the elderly, and patients with cardiopulmonary disorders or immunocompromised states, cause severe manifestations which often result in fatalities. the emergence of a new antigen type of influenza a virus (h5n1) in hong kong during 1997 and 1998 threatened a possible pandemic of a new influenza infection. the investigation for anti-influenza chemotherapies has progressed in the last decade whereas clinical trials of new compou ...199910641217
vaccines against h5n1 influenza. 199910660430
characterization of the pathogenicity of members of the newly established h9n2 influenza virus lineages in asia.the reported transmission of avian h9n2 influenza viruses to humans and the isolation of these viruses from hong kong poultry markets lend urgency to studies of their ecology and pathogenicity. we found that h9n2 viruses from north america differ from those of asia. the north american viruses, which infect primarily domestic turkeys, replicated poorly in inoculated chickens. phylogenetic analysis of the hemagglutinin and nucleoprotein genes indicated that the asian h9n2 influenza viruses could b ...200010662623
genetic analysis of the compatibility between polymerase proteins from human and avian strains of influenza a order to determine how efficiently the polymerase proteins derived from human and avian influenza a viruses can interact with each other in the context of a mammalian cell, a genetic system that allows the in vivo reconstitution of active ribonucleoproteins was used. the ability to achieve replication of a viral-like reporter rna in cos-1 cells was examined with heterospecific mixtures of the core proteins (pb1, pb2, pa and np) from two strains of human viruses (a/puerto rico/8/34 and a/victo ...200010769071
evolutionary characterization of the six internal genes of h5n1 human influenza a virus.the entire nucleotide sequences of all six internal genes of six human h5n1 influenza a viruses isolated in hong kong in 1997 were analysed in detail from a phylogenetic point of view and compared with the evolutionary patterns of the haemagglutinin and neuraminidase genes. despite being isolated within a single year in the same geographical location, human h5n1 viruses were characterized by a variety of amino acid substitutions in the ribonucleoprotein complex [pb2, pb1, pa and nucleoprotein (n ...200010769072
global epidemiology of influenza: past and present.pandemics are the most dramatic presentation of influenza. three have occurred in the twentieth century: the 1918 h1n1 pandemic, the 1957 h2n2 pandemic, and the 1968 h3n2 pandemic. the tools of molecular epidemiology have been applied in an attempt to determine the origin of pandemic viruses and to understand what made them such successful pathogens. an excellent example of this avenue of research is the recent phylogenetic analysis of genes of the virus that caused the devastating 1918 pandemic ...200010774473
strategies for inducing protection against avian influenza a virus subtypes with dna vaccines.the cross-species transfer of a h5n1 influenza virus from birds to humans, and the systemic spread of this virus in mice, has accelerated the efforts to devise protective strategies against lethal influenza viruses. dna vaccination with the highly conserved nucleoprotein gene appears to provide cross protection against influenza a viruses in murine models. whether such vaccines would protect human hosts against different influenza a viruses, including strains with pandemic potential, is unclear. ...200010775793
pandemic influenza is a zoonosis, as it requires introduction of avian-like gene segments in the human population.human influenza viruses manage to cause epidemics almost every year. the circulating viruses change their surface glycoproteins by accumulating mutations (antigenic drift) which results in variant viruses of the same subtype that are able to evade the immune pressure in the population. every now and then, a completely new subtype of influenza a virus is introduced in the human population, which can result in an influenza pandemic. pandemic human influenza viruses have been emerging for many cent ...200010799785
interspecies transmission of influenza viruses: h5n1 virus and a hong kong sar perspective.this account takes stock of events and involvements, particularly on the avian side of the influenza h5n1 'bird flu' incident in hong kong sar in 1997. it highlights the role of the chicken in the many live poultry markets as the source of the virus for humans. the slaughter of chicken and other poultry across the sar seemingly averted an influenza pandemic. this perspective from hong kong sar marks the coming-of-age of acceptance of the role of avian hosts as a source of pandemic human influenz ...200010799786
depletion of lymphocytes and diminished cytokine production in mice infected with a highly virulent influenza a (h5n1) virus isolated from humans.previously, we observed that several virulent influenza a (h5n1) viruses which caused severe or fatal disease in humans were also lethal in balb/c mice following dissemination of the virus to solid organs, including the brain. in contrast, one particular human h5n1 virus was nonlethal in mice and showed no evidence of systemic spread. to compare h5n1 viruses of varying pathogenicity for their ability to alter the mammalian immune system, mice were infected with either influenza a/hong kong/483/9 ...200010846094
characterization of the influenza a virus gene pool in avian species in southern china: was h6n1 a derivative or a precursor of h5n1?in 1997, an h5n1 influenza virus outbreak occurred in chickens in hong kong, and the virus was transmitted directly to humans. because there is limited information about the avian influenza virus reservoir in that region, we genetically characterized virus strains isolated in hong kong during the 1997 outbreak. we sequenced the gene segments of a heterogeneous group of viruses of seven different serotypes (h3n8, h4n8, h6n1, h6n9, h11n1, h11n9, and h11n8) isolated from various bird species. the p ...200010864640
continued circulation in china of highly pathogenic avian influenza viruses encoding the hemagglutinin gene associated with the 1997 h5n1 outbreak in poultry and humans.since the outbreak in humans of an h5n1 avian influenza virus in hong kong in 1997, poultry entering the live-bird markets of hong kong have been closely monitored for infection with avian influenza. in march 1999, this monitoring system detected geese that were serologically positive for h5n1 avian influenza virus, but the birds were marketed before they could be sampled for virus. however, viral isolates were obtained by swabbing the cages that housed the geese. these samples, known collective ...200010864673
pathogenesis of and immunity to avian influenza a h5 1997 in hong kong, 18 human cases of respiratory illness were caused by an avian influenza a h5n1 virus. although avian influenza viruses had not previously been known to cause respiratory illness in humans, the h5n1 viruses caused severe illness and death, primarily in individuals aged > 12 years. the introduction of h5n1 viruses into humans raised concerns about the potential of these viruses to cause a pandemic. we have used the balb/c mouse to better understand the pathogenesis of and imm ...200010872716
characterization of low virulent strains of highly pathogenic a/hong kong/156/97 (h5n1) virus in mice after passage in embryonated hens' eggs.avian influenza a h5n1 viruses were isolated from humans for the first time in hong kong in 1997. the virulence of a/hong kong/156/97 (hk156) strain in mice was found to change significantly depending on the passage history of the virus. madin-darby canine kidney (mdck) cell-grown parental virus and three of its clones derived from mouse brain showed high pathogenicity in mice after intranasal or intracerebral infection. in contrast, the egg-derived parental virus hk156-e3 and its cloned viruses ...200010873787
a simple restriction fragment length polymorphism-based strategy that can distinguish the internal genes of human h1n1, h3n2, and h5n1 influenza a viruses.a simple molecular technique for rapid genotyping was developed to monitor the internal gene composition of currently circulating influenza a viruses. sequence information from recent h1n1, h3n2, and h5n1 human virus isolates was used to identify conserved regions within each internal gene, and gene-specific pcr primers capable of amplifying all three virus subtypes were designed. subtyping was based on subtype-specific restriction fragment length polymorphism (rflp) patterns within the amplifie ...200010878047
precursor genes of future pandemic influenza viruses are perpetuated in ducks nesting in siberia.influenza a viruses of different subtypes were isolated from fecal samples of ducks in their nesting areas in siberia in summer from 1996 to 1998. phylogenetic analysis of the np genes of the isolates in siberia and those in hokkaido, japan on their flyway of migration from siberia to the south in autumn revealed that they belong to the eurasian lineage of avian influenza viruses. it is noted that the genes of the isolates in siberia are closely related to those of h5n1 influenza virus strains i ...200010881676
[development of influenza vaccines against newly emerging a/h5n1 virus].emergence of highly virulent influenza a/h5n1 viruses in hong kong in 1997 posed a threat of pandemic and brought an urgent need to develop a suitable seed virus for vaccine production. the virulence of the h5n1 viruses to chicken embryos should hamper the efficient production of the vaccine. in addition, potential virulence to humans raised safety issue in manufacturing vaccine. toward vaccine development, one approach is to use an avirulent avian influenza virus antigenically similar to the vi ...200010885322
influenza virus: a master of metamorphosis.novel influenza viruses continuously emerge in the human population. three times during the present century, an avian influenza virus subtype crossed the species barrier, starting a pandemic, and establishing itself for one to several decades in man. as the 1997 h5n1 event in hong kong indicated, the occurrence of another pandemic in the near future cannot be excluded. sufficient vaccine may not be available to ameliorate the consequences of such an event, because of a shortage of time. during i ...200010908015
avian-to-human transmission of h9n2 subtype influenza a viruses: relationship between h9n2 and h5n1 human 1997, 18 cases of influenza in hong kong (bird flu) caused by a novel h5n1 (chicken) virus resulted in the deaths of six individuals and once again raised the specter of a potentially devastating influenza pandemic. slaughter of the poultry in the live bird markets removed the source of infection and no further human cases of h5n1 infection have occurred. in march 1999, however, a new pandemic threat appeared when influenza a h9n2 viruses infected two children in hong kong. these two virus is ...200010920197
characterization of human influenza a (h5n1) virus infection in mice: neuro-, pneumo- and adipotropic infection.mice (ddy strain, 4 weeks old) were infected intranasally with the h5n1 influenza viruses a/hong kong/156/97 (hk156) and a/hong kong/483/97 (hk483) isolated from humans. hk156 and hk483 required 200 and 5 p.f.u. of virus, respectively, to give a 50% lethal dose to the mice when the volume of inoculum was set at 10 microl. both viruses caused encephalitis and severe bronchopneumonia in infected mice. the severity of lung lesions caused by the viruses was essentially similar, whereas hk483 caused ...200010993940
h9n2 influenza viruses possessing h5n1-like internal genomes continue to circulate in poultry in southeastern china.the transmission of h9n2 influenza viruses to humans and the realization that the a/hong kong/156/97-like (h5n1) (abbreviated hk/156/97) genome complex may be present in h9n2 viruses in southeastern china necessitated a study of the distribution and characterization of h9n2 viruses in poultry in the hong kong sar in 1999. serological studies indicated that h9n2 influenza viruses had infected a high proportion of chickens and other land-based birds (pigeon, pheasant, quail, guinea fowl, and chukk ...200011000205
molecular aspects of avian influenza (h5n1) viruses isolated from 1997, 18 human infections with h5n1 influenza type a were identified in hong kong and six of the patients died. there were concomitant outbreaks of h5n1 infections in poultry. the gene segments of the human h5n1 viruses were derived from avian influenza a viruses and not from circulating human influenza a viruses. in 1999 two cases of human infections caused by avian h9n2 virus were also identified in hong kong. these events established that avian influenza viruses can infect humans without p ...200011015744
heterologous protection against lethal a/hongkong/156/97 (h5n1) influenza virus infection in c57bl/6 mice.the continual threat posed by newly emerging influenza virus strains is demonstrated by the recent outbreak of h5n1 influenza virus in hong kong. currently, immunization against influenza virus infection is fairly adequate, but it is imperative that improved vaccines are developed that can protect against a variety of strains and be generated rapidly. since humoral immunity is ineffective against serologically distinct viruses, one strategy would be to develop vaccines that emphasize cellular im ...200011038381
molecular correlates of influenza a h5n1 virus pathogenesis in mice.highly pathogenic avian influenza a h5n1 viruses caused an outbreak of human respiratory illness in hong kong. of 15 human h5n1 isolates characterized, nine displayed a high-, five a low-, and one an intermediate-pathogenicity phenotype in the balb/c mouse model. sequence analysis determined that five specific amino acids in four proteins correlated with pathogenicity in mice. alone or in combination, these specific residues are the likely determinants of virulence of human h5n1 influenza viruse ...200011044127
h9n2 subtype influenza a viruses in poultry in pakistan are closely related to the h9n2 viruses responsible for human infection in hong kong.following the outbreak of h5n1 "bird flu" in hong kong in 1997, the isolation of h9n2 subtype viruses from patients in southern china and hong kong sar once again raised the spectre of a possible influenza pandemic. h9n2 viruses have recently been responsible for disease in poultry in various parts of the world and preliminary studies of the h9 haemagglutinin (ha) genes of viruses isolated during 1998 and 1999 in germany, iran, pakistan, and saudi arabia showed a close relationship to the ha gen ...200011112478
influenza virus (a/hk/156/97) hemagglutinin expressed by an alphavirus replicon system protects chickens against lethal infection with hong kong-origin h5n1 viruses.venezuelan equine encephalitis virus replicon particles (vrp) containing the gene expressing hemagglutinin (ha) from the human hong kong influenza a isolate (a/hk/156/97) were evaluated as vaccines in chicken embryos and young chicks. expressed ha was readily detected in bird-tissue staining with anti-h5 ha antibody and in chicken cells infected with the replicon preparations following immunoprecipitation with monoclonal antibody. birds challenged with a dose of the lethal parent virus were prot ...200011112481
the neuraminidase inhibitor gs4104 (oseltamivir phosphate) is efficacious against a/hong kong/156/97 (h5n1) and a/hong kong/1074/99 (h9n2) influenza 1997, an h5n1 avian influenza a/hong kong/156/97 virus transmitted directly to humans and killed six of the 18 people infected. in 1999, another avian a/hong/1074/99 (h9n2) virus caused influenza in two children. in such cases in which vaccines are unavailable, antiviral drugs are crucial for prophylaxis and therapy. here we demonstrate the efficacy of the neuraminidase inhibitor gs4104 (oseltamivir phosphate) against these h5n1 and h9n2 viruses. gs4071 (the active metabolite of oseltamivir) ...200011114412
avian influenza viruses infecting humans.avian species, particularly waterfowl, are the natural hosts of influenza a viruses. influenza viruses bearing each of the 15 hemagglutinin and nine neuraminidase subtypes infect birds and serve as a reservoir from which influenza viruses or genes are introduced into the human population. viruses with novel hemagglutinin genes derived from avian influenza viruses, with or without other accompanying avian influenza virus genes, have the potential for pandemic spread when the human population lack ...200011130181
pandemic threat posed by avian influenza a viruses.influenza pandemics, defined as global outbreaks of the disease due to viruses with new antigenic subtypes, have exacted high death tolls from human populations. the last two pandemics were caused by hybrid viruses, or reassortants, that harbored a combination of avian and human viral genes. avian influenza viruses are therefore key contributors to the emergence of human influenza pandemics. in 1997, an h5n1 influenza virus was directly transmitted from birds in live poultry markets in hong kong ...200111148006
pathology of fatal human infection associated with avian influenza a h5n1 virus.eighteen cases of human influenza a h5n1 infection were identified in hong kong from may to december 1997. two of the six fatal cases had undergone a full post-mortem which showed reactive hemophagocytic syndrome as the most prominent feature. other findings included organizing diffuse alveolar damage with interstitial fibrosis, extensive hepatic central lobular necrosis, acute renal tubular necrosis and lymphoid depletion. elevation of soluble interleukin-2 receptor, interleukin-6 and interfero ...200111170064
implication of the proprotein convertases furin, pc5 and pc7 in the cleavage of surface glycoproteins of hong kong, ebola and respiratory syncytial viruses: a comparative analysis with fluorogenic peptides.fluorogenic peptides encompassing the processing sites of envelope glycoproteins of the infectious influenza a hong kong virus (hkv), ebola virus (ebov) and respiratory syncytial virus (rsv) were tested for cleavage by soluble recombinants of the proprotein convertases furin, pc5 and pc7. kinetic studies with these intramolecularly quenched fluorogenic peptides revealed selective cleavages at the physiological dibasic sites. the hkv peptide is cleaved by both furin and pc5 with similar efficacy; ...200111171050
characterization of h5n2 influenza viruses from italian poultry.from october 1997 to january 1998, highly pathogenic h5n2 avian influenza viruses caused eight outbreaks of avian influenza in northern italy. a nonpathogenic h5n9 influenza virus was also isolated during the outbreaks as a result of virological and epidemiological surveillance to control the spread of avian influenza to neighbouring regions. antigenic analysis showed that the italian h5n2 isolates were antigenically similar to, although distinguishable from, a/hk/156/97, a human influenza h5n1 ...200111172104
cyclopentane neuraminidase inhibitors with potent in vitro anti-influenza virus activities.a novel series of cyclopentane derivatives have been found to exhibit potent and selective inhibitory effects on influenza virus neuraminidase. these compounds, designated rwj-270201, bcx-1827, bcx-1898, and bcx-1923, were tested in parallel with zanamivir and oseltamivir carboxylate against a spectrum of influenza a (h1n1, h3n2, and h5n1) and influenza b viruses in mdck cells. inhibition of viral cytopathic effect ascertained visually and by neutral red dye uptake was used, with 50% effective ( ...200111181354
recent zoonoses caused by influenza a viruses.influenza is a highly contagious, acute illness which has afflicted humans and animals since ancient times. influenza viruses are part of the orthomyxoviridae family and are grouped into types a, b and c according to antigenic characteristics of the core proteins. influenza a viruses infect a large variety of animal species, including humans, pigs, horses, sea mammals and birds, occasionally producing devastating pandemics in humans, such as in 1918, when over twenty million deaths occurred worl ...200011189716
cross-reactive, cell-mediated immunity and protection of chickens from lethal h5n1 influenza virus infection in hong kong poultry 1997, avian h5n1 influenza virus transmitted from chickens to humans resulted in 18 confirmed infections. despite harboring lethal h5n1 influenza viruses, most chickens in the hong kong poultry markets showed no disease signs. at this time, h9n2 influenza viruses were cocirculating in the markets. we investigated the role of h9n2 influenza viruses in protecting chickens from lethal h5n1 influenza virus infections. sera from chickens infected with an h9n2 influenza virus did not cross-react wi ...200111222674
[mechanism of the emergence of pandemic influenza virus strains and their control measures].the 1957 asian h2n2 and 1968 hong kong h3n2 pandemic strains of influenza are genetic reassortants between avian viruses and human strains. since avian viruses of any subtype can contribute genes in the generation of reassortants in pigs, none of the 15 ha and 9 na subtypes can be ruled out as potential candidates for future pandemics. the h5n1 influenza virus transmission from domestic poultry to humans in hong kong in 1997 further emphasized the need to have information on influenza viruses in ...200011225307
[influenza live attenuated vaccine].inactivated influenza vaccine has been widely used; however, its effectiveness is not always perfect. to create a much better vaccine, live vaccines have been extensively investigated. among several candidate live vaccines, cold-adapted(ca) vaccine is the only promising candidate. according to clinical studies recently conducted in the u.s., ca vaccine was proven to be highly effective against laboratory confirmed influenza, both in adults and children. furthermore, ca vaccines for the h5n1 pand ...200011225322
imported parakeets harbor h9n2 influenza a viruses that are genetically closely related to those transmitted to humans in hong 1997 and 1998, h9n2 influenza a viruses were isolated from the respiratory organs of indian ring-necked parakeets (psittacula krameri manillensis) that had been imported from pakistan to japan. the two isolates were closely related to each other (>99% as determined by nucleotide analysis of eight rna segments), indicating that h9n2 viruses of the same lineage were maintained in these birds for at least 1 year. the hemagglutinins and neuraminidases of both isolates showed >97% nucleotide ident ...200111238878
efficacy of zanamivir against avian influenza a viruses that possess genes encoding h5n1 internal proteins and are pathogenic in 1997, an avian h5n1 influenza virus, a/hong kong/156/97 (a/hk/156/97), caused six deaths in hong kong, and in 1999, an avian h9n2 influenza virus infected two children in hong kong. these viruses and a third avian virus [a/teal/hk/w312/97 (h6n1)] have six highly related genes encoding internal proteins. additionally, a/chicken/hk/g9/97 (h9n2) virus has pb1 and pb2 genes that are highly related to those of a/hk/156/97 (h5n1), a/teal/hk/w312/97 (h6n1), and a/quail/hk/g1/97 (h9n2) viruses. becau ...200111257037
pathobiology of a/chicken/hong kong/220/97 (h5n1) avian influenza virus in seven gallinaceous bird-to-human transmission, with the production of severe respiratory disease and human mortality, is unique to the hong kong-origin h5n1 highly pathogenic avian influenza (hpai) virus, which was originally isolated from a disease outbreak in chickens. the pathobiology of the a/chicken/hong kong/220/97 (h5n1) (hk/220) hpai virus was investigated in chickens, turkeys, japanese and bobwhite quail, guinea fowl, pheasants, and partridges, where it produced 75-100% mortality within 10 days. de ...200111280371
mucosal delivery of inactivated influenza vaccine induces b-cell-dependent heterosubtypic cross-protection against lethal influenza a h5n1 virus infection.influenza vaccines that induce greater cross-reactive or heterosubtypic immunity (het-i) may overcome limitations in vaccine efficacy imposed by the antigenic variability of influenza a viruses. we have compared mucosal versus traditional parenteral administration of inactivated influenza vaccine for the ability to induce het-i in balb/c mice and evaluated a modified escherichia coli heat-labile enterotoxin adjuvant, lt(r192g), for augmentation of het-i. mice that received three intranasal (i.n. ...200111333895
pattern of mutation in the genome of influenza a virus on adaptation to increased virulence in the mouse lung: identification of functional themes.the genetic basis for virulence in influenza virus is largely unknown. to explore the mutational basis for increased virulence in the lung, the h3n2 prototype clinical isolate, a/hk/1/68, was adapted to the mouse. genomic sequencing provided the first demonstration, to our knowledge, that a group of 11 mutations can convert an avirulent virus to a virulent variant that can kill at a minimal dose. thirteen of the 14 amino acid substitutions (93%) detected among clonal isolates were likely instrum ...200111371620
the leeuwenhoek lecture 2001. animal origins of human infectious disease.since time immemorial animals have been a major source of human infectious disease. certain infections like rabies are recognized as zoonoses caused in each case by direct animal-to-human transmission. others like measles became independently sustained with the human population so that the causative virus has diverged from its animal progenitor. recent examples of direct zoonoses are variant creutzfeldt-jakob disease arising from bovine spongiform encephalopathy, and the h5n1 avian influenza out ...200111405946
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