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the infection of ferrets with swine influenza virus.the experiments described confirm the earlier observation of smith, andrewes, and laidlaw that the swine influenza virus is pathogenic for ferrets when administered intranasally. a disease that is clinically more severe and pathologically more extensive than that described by the above workers is obtained if inoculation with the virus is performed under ether anesthesia. animals infected in this way show at autopsy an edematous type of pneumonia of lobar distribution which may terminate fatally. ...193419870285
the infection of mice with swine influenza virus.the experiments confirm the earlier observation of andrewes, laidlaw and smith that the swine influenza virus is pathogenic for white mice when administered intranasally. two field strains of the swine influenza virus were found to differ in their initial pathogenicity for mice. one strain was apparently fully pathogenic even in its 1st mouse passage while the other required 2 or 3 mouse passages to acquire full virulence for this species. both strains, however, were initially infectious for mic ...193519870434
immunization experiments with swine influenza virus.1. swine influenza virus obtained from the lungs of infected ferrets or mice, when administered intramuscularly or subcutaneously, immunizes swine to swine influenza. 2. ferrets, which have received subcutaneous injections of swine influenza virus obtained from the lungs of infected ferrets, are immune to intranasal infection with this virus. similar injections with virus from the lungs of infected mice or swine do not immunize. 3. mice can be immunized to intranasal infection with swine influen ...193619870522
quantitative aspects of homologous and heterologous active immunity to strains of the virus of epidemic influenza.when mice are immunized by one intraperitoneal inoculation with active or inactive influenza virus (strain pr8, w.s., and melbourne) the quantity required for protection against heterologous strains is about 10 times the homologous minimal immunizing dose. three injections increase the immunity to all strains, but the ratio between the homologous and heterologous minimal immunizing dose is not altered. swine influenza virus given intraperitoneally fails to immunize against human strains unless t ...194019871048
studies on influenza virus : the complement-fixing antigen of influenza a and swine influenza viruses.influenza complement fixation tests designed for use with ferret serum are described. complement-fixing antigens derived from influenza ferret lungs were unsatisfactory due to their low content of soluble antigen; those prepared from mouse lungs or developing chick embryo membranes proved to be better antigenically and were reliable when the various reagents in the test were properly adjusted to eliminate non-specific fixation of complement. the results of cross complement fixation tests indicat ...194119871098
the quantitative determination of influenza virus and antibodies by means of red cell agglutination.1. the agglutination titer for chicken red cells of freshly prepared or carefully stored suspensions of pr8 influenza virus, that is to say virus of maximum pathogenicity, was found to be proportional to the mouse lethal titer of the same preparations. 2. the agglutination titer of infected allantoic fluid procured in a standard way is relatively constant, regardless of the influenza strain used and its pathogenicity for mice. 3. virus preparations inactivated by heat or storage may retain their ...194219871167
antigenic relationship of british swine influenza strains to standard human and swine influenza viruses : the use of chicken and ferret antisera in red cell agglutination.the antigenic relationships of type a (pr 8, ws) and type b (lee) human strains and the shope and british (cambridge, north ireland) swine strains were studied by specific antiserum inhibition of chicken red cell agglutination by the influenza virus. the cambridge and north ireland strains were found to be closely related to the type a strains and differentiated from the shope virus. the distinctive antigenicity of the lee strain of type b was confirmed. specific antibodies were developed in chi ...194319871297
studies of antigenic differences among strains of influenza a by means of red cell agglutination.a study of cross inhibition tests among strains of influenza a virus and their antisera showed that the results obtained were subject to a certain amount of variation due to the red cells, the virus suspensions, and the ferret antisera employed. methods have been demonstrated for handling the data obtained from such tests, so that these variables were corrected or avoided, making it possible to use the agglutination technique for antigenic comparisons. the antigenic pattern of eighteen strains o ...194319871338
qualitative differences in the antigenic composition of influenza a virus strains.a study of the pr8, christie, talmey, w.s., and swine strains of influenza a virus by means of antibody absorption tests revealed the following findings: 1. serum antibody could be specifically absorbed with allantoic fluid containing influenza virus or, more effectively, with concentrated suspensions of virus obtained from allantoic fluid by high-speed centrifugation or by the red cell adsorption and elution technique. normal allantoic fluid, or the centrifugalized sediment therefrom, failed to ...194419871392
significance of antigenic differences among strains of influenza a virus in reinfection of ferrets. 194620274239
adrenocorticotrophic hormone (acth) in the treatment of experimental air-borne influenza virus type a infection in the ferret. 195114824691
tissue tropism of a strain of influenza a virus in ferrets. 195513233518
studies on influenza infection in ferrets by means of fluorescein-labelled antibody. ii. the role of soluble antigen in nuclear fluorescence and cross-reactions.yellow-green fluorescence representing viral antigens was detected in both the nucleus and cytoplasm of epithelial cells of the respiratory tract in ferrets infected with influenza virus. this nuclear fluorescence was the chief manifestation of cross-fluorescent staining reactions among three strains of influenza a virus studied, pr8, farrington, and fm(1). absorption experiments with influenza viral v and soluble s antigens showed that s antigen was responsible for the presence of fluorescence ...195514367688
antigenic variants of influenza a virus (pr8 strain). v. virulence, antigenic potency, and cross-protection tests in mice of the original and second series.two series of variants of influenza pr8-s virus have been described. while all retain the same degree of pathogenicity for mice and fertile eggs, there was a progressive loss in the ability of the variants to provoke antibody following vaccination or infection of mice and ferrets. the immunogenicity of the variants was, therefore, less than that of the original strain. although little or no serological relationship could be demonstrated between some of the variants and the pr8-s virus a consider ...195813539310
[studies on the virusemia in ferrets infected with the influenza virus a-1]. 196414198514
effect of caffeic acid on mouse and ferret lung infected with influenza a virus. 19654286922
response of ferrets and monkeys to intranasal infection with human, equine and avian influenza viruses.rhesus monkeys and ferrets were exposed to intranasal inoculation of several strains of egg-adapted avian, equine and human influenza viruses and to strains of mouse-adapted equine influenza viruses. local replication of virus and seroconversion were observed in the majority of these animals. however, clinical infection was observed only in ferrets.19714251419
antigenic properties of the envelope of influenza virus rendered soluble by surfactant-solvent systems.dissociating chemical treatments employing surfactant-solvent systems were applied to purified influenza a and b viruses to obtain viral preparations possessing a significantly higher or lower haemagglutinating activity than the intact virus. all preparations, whether with high or low haemagglutinating activity, with the exception of envelope protein solubilized by triton x-100, were significantly lacking in the ability to excite the formation of haemagglutination-inhibiting and virus-neutralizi ...19715291750
antigenic relationship between influenza b viruses.the object of this study was to determine whether antigenic groupings exist among influenza b viruses. altogether, 22 influenza type b strains isolated during the years 1940-68 were examined by reciprocal haemagglutination-inhibition, strain-specific complement-fixation, and serum neutralization tests with sera produced in ferrets and guinea-pigs. it was found that the strain-specific complement-fixation test was superior for separating influenza b viruses into groups whereas the haemagglutinati ...19715317011
comparison of neutralizing activity in nasal secretion and serum of ferrets in response to infection with influenza a viruses. 19734692625
immunization of ferrets against influenza: a comparison of killed ferret grown and egg grown virus. 19744422501
immunity to influenza in ferrets. vii. effect of previous infection with heterotypic and heterologous influenza viruses on the response of ferrets to inactivated influenza virus vaccines.normal ferrets did not produce serum antibody following immunization with 200 i.u. of inactivated a/hong kong/68 influenza virus vaccine and were found to be susceptible to subsequent challenge infection with a/hong kong/68 virus. high titres of virus were recovered from nasal washings collected 3 days after infection, serum antibody was produced, increased nasal protein was detected and hi antibody was detected in nasal washings. ferrets infected with influenza virus a/pr/8/34 7 weeks before im ...19744522247
immunity to influenza in ferrets. xi. cross-immunity between a/hong kong/68 and a/england/72 viruses: serum antibodies produced by infection or immunization.the degree of immunity due to cross-reactions between antibody to influenza virus a/hong kong/1/68 and a/england/42/72 was studied in ferrets. ferrets were immunized with the viruses by either live infection or by inoculation with inactivated virus vaccines. the vaccines were given with freund's incomplete adjuvant or were given to ferrets previously infected with influenza virus a/pr/8/34. as a result of these immunizations the animals all produced similar titres of serum hi antibody to the imm ...19744531448
immunity to influenza in ferrets. x. intranasal immunization of ferrets with inactivated influenza a virus vaccines.the response of ferrets after intranasal inoculation of inactivated a/hong kong/68 (h3n2) influenza virus vaccines is reported. normal ferrets given either saline vaccine in drops or freeze-dried vaccine in an aerosol intranasally did not produce detectable serum or nasal hemagglutination inhibiting antibody and were found to be completely susceptible to challenge infection with a/hong kong/68 virus. intranasal saline vaccine did not produce an additive effect on the response of ferrets simultan ...19744830530
replication of influenza virus in organ cultures of human and simian urogenital tissues and human foetal tissues.a survey of human adult tissues in organ cultures showed that influenza viruses (a/moscow/1019/65 (h2n2) or a recombinant virus virulent for man (pr/8-a/england/939/69 clone 7a(h3n2)) could infect uterus, bladder and conjunctiva but not oesophagus under the conditions employed; simian bladder and uterus were also susceptible. these results were similar to those already described for corresponding ferret tissues. organ cultures of human foetal nasal mucosa, trachea, oesophagus, small and large in ...1975809051
assessment of resistance to influenza virus infection in animal models.the antibody response and immunity to challenge infection were determined in ferrets immunized with inactivated influenza vaccine in saline or adjuvant. adjuvanated vaccines induced variable titres of serum antibody, and the degree of immunity to challenge infection was directly related to the titre of serum hi antibody induced by these vaccines. conventional doses of saline vaccine did not induce serum hi antibody, and the ferrets were completely susceptible to challenge infection. infection wi ...19751126574
an 'in vitro' marker of attenuation for live influenza virus vaccine candidates.organ cultures of ferret tracheal rings maintained in tubes for up to two months supported the growth of several strains of influenza a viruses produced by genetic recombination. these strains were developed as possible candidates for live attenuated influenza virus vaccines. by observing the effects on cilia and titrating the growth in eggs it was possible to rank these various influenza strains in order of descending virulence for the respiratory epithelium in organ culture. this rank correspo ...19751126579
the behaviour in ferrets of two closely related clones of influenza virus of differing virulence for man.clones 7a and 64d of the recombinant influenza virus a/pr/8/34-a/england/939/69(h3n2) which are of different virulence for man as judged by clinical score (7a more virulent than 64d) showed similar differences in ferrets. with intranasal inoculation the approximate 50% minimal infectious doses of both clones were similar (between 10(0) and 10(2) eid(50)) as were their titres in nasal washes 24 h after inoculation and the histologically evident damage they caused in the nasal turbinates. however, ...19761268040
production of highly cross-reactive hemagglutination-inhibiting influenza antibodies in ferrets.ferrets were sequentially infected at time intervals of 3 weeks with different influenza virus a strains. it was found that secondary infection can result in the appearance of antibodies highly cross-reacting with a virus strain closely related to the strain of first infection. such highly cross-reacting antibodies were designated as hcr antibodies. evidence is presented that hcr antibodies were not antineuraminidase antibodies and, in addition, were not specifically oriented to the strain with ...19761278996
evaluation of 6-azauridine and 5-iododeoxyuridine in the treatment of experimental viral infections.the potential antiviral activity of 6-azauridine and 5-iododeoxyuridine was evaluated in a coordinated study at five institutions. experimental models in five species, the mouse, rabbit, swine, cat, and ferret, were established with use of 10 viruses: herpesvirus hominis types 1 and 2, murine cytomegalovirus, vaccinia virus, shope fibroma virus, transmissible gastroenteritis virus, swine influenza virus, feline viral rhinotracheitis virus, feline panleukopenia virus, and ferret distemper virus. ...1976180189
antigenic variants of influenza a virus obtained in vitro.the aim of this study was to investigate antigenic "drift" in the haemagglutinin and neuraminidase antigens of influenza a virus in vitro under immunological pressure. variants of the "asian" influenza strains a/england/12/64 (h2n2) and a/tokyo/3/67 (h2n2) were isolated in the allantois-on-shell system in the presence of homologous postinfection ferret sera. for each of these two viruses three generations of variants were isolated and characterized. it was found that the successive antigenic var ...197662624
behaviour in ferrets of swine influenza virus isolated from man.after intranasal instillation into ferrets, the "swine" influenza virus a/new jersey/8/76(hsw1 n1) had a 50% minimal infectious dose similar to that of previously tested a/pr/8-a/england (h3 n2) recombinants virulent and attenuated for man. a/new jersey produced only a mild upper respiratory tract infection. however, higher titres of virus were recovered from the lungs over a longer period than experienced previously with asian and hong kong virus strains. there was a diphasic pyrexia the second ...197763712
antigenic subgroups of influenza a (hsw1 n1) virus differentiated by hemagglutination inhibition.eleven influenza a/swine virus strains could be arranged in three subgroups by hemagglutination inhibition (hi) titrations. the antisera used include post-infection ferret sera (native as well as after adsorption with heterologous hsw1 n1 virus) and paired human sera from recent influenza a patients, showing antibody titre rises against a/swine virus. for serological detection of infections with an unknown a/swine virus, virus strains of the subgroup with the broadest reactivity are more suitabl ...1977604129
protective efficacy of rit 4025, a live attenuated influenza vaccine strain, and evaluation of heterotypic immunity to influenza a viruses in ferrets.ferrets immunized with an h3n2 recombinant of a/pr/8/34 and a/scotland/840/74 (rit 4025 vaccine strain) were almost completely protected against a challenge with the homologous strain a/scotland/840/74. the protection was lower but highly significant when the challenge was performed with the heterologous a/victoria/3/75 wild strain. the protection afforded by the vaccine strain was measured by three indicators: absence of temperature rise, absence or reduction of virus shedding and absence or re ...1977269196
temperature-sensitive mutants of influenza virus. xiii. evaluation of influenza a/hong kong/68 and a/udorn/72 ts and wild-type viruses in tracheal organ culture at permissive and restrictive temperatures.for development of an in vitro assay of attenuation for virus vaccine candidates, tracheal ring organ cultures from young ferrets were infected with influenza a/hong kong/68 and a/udorn/72 temperature-sensitive (ts) recombinant and wild-type viruses and observed for 21 days at permissive (33 c) and restrictive (37 c) temperatures for effects on ciliated epithelium and viral replication. results were compared with the known effects of these viruses in humans. viruses that damaged ferret cilia and ...1977886200
differential response of ferrets to infection with virulent and avirulent influenza viruses: a possible marker of virus attenuation. 1977921544
specific immunity to influenza virus in ferret organ cultures.ferret tracheal organ cultures prepared from animals previously infected intranasally with influenza a virus required approximately 130 times more homologous virus (a/pr/8/34(hon1) or a/port chalmers/1/73 (h3n2)) to become infected in vitro than similar cultures from normal ferrets. also, these cultures from convalescent ferrets required 9 times more heterologous virus (a/pr/8/34(hon1) or sendai) to become infected in vitro than similar cultures from normal animals challenged in vitro with the h ...1978638028
temperature-sensitive mutants of influenza a virus: production and characterization of a/victoria/3/75-ts-1[e] recombinants.the hong kong/68-ts-1[e] virus, which has a 38 degrees c shutoff temperature for plaque formation, has been proposed as a donor of its two ts lesions to new variants of influenza a virus that pose an epidemic threat. to further examine whether the acquisition of the two ts-1[e] lesions will predictably attenuate new influenza a variants, the hk/68-ts-1[e] virus was mated with the a/vic/3/75 wild-type virus. the vic/75-ts-[e] recombinants that had the two ts-1[e] lesions also had a 38 degrees c s ...1978669818
scanning and transmission electron microscopy study of ferret respiratory mucosa infected with influenza a virus.the use of both sem and tem techniques in studying the alterations of the columnar ciliated epithelium of the whole respiratory tract of ferrets enables the authors to find a significant discrepancy between tracheal and nasal mucosa destructions. this discrepancy is not a function of the anatomical location of virus instillation. theoretical and pratical meanings are discussed.1978677615
co-circulation of two influenza a (h3n2) antigenic variants detected by virus surveillance in individual communities.from march through june 1977 a total of 31 influenza a (h3n2) viruses were isolated from students with respiratory disease who were seen at the student health service on the berkeley campus of the university of california, and 32 influenza a (h3n2) viruses were isolated from persons who participated in a city-wide febrile respiratory disease surveillance program in seattle. the antigenic specificity of the hemagglutinin was determined for each isolate by hemagglutination inhibition testing with ...197883107
antigenic relationship between influenza c viruses.the object of this study was to determine whether antigenic groupings exist among influenza c viruses. altogether seven influenza type c strains were examined by reciprocal haemagglutination-inhibition and serum neutralization tests with sera produced in ferrets. some biological properties were also compared and differences were found in their ability to agglutinate erythrocytes from various species, in their ability to adsorb onto rat and fowl erythrocytes, and in their rates of elution from th ...1978104696
further studies of the antigenic properties of h3n2 strains of influenza a isolated from swine in south east asia.h3n2 strains of influenza a isolated from swine in hong kong were compared with human strains of h3n2 influenza a variants in reciprocal hi tests using ferret sera. one isolate from swine was indistinguishable from a/hong kong/68, one set of viruses isolated in 1976 and 1977 was most related to a/hong kong/68 but was not identical to it, two isolates from 1976 were 'bridging strains' that cross-reacted equally with the contemporary variants a/victoria/3/75 and a/texas/1/77, similarly to a small ...197991663
comparison of sevral wild-type influenza viruses in the ferret tracheal organ culture system.several strains of wild-type influenza a virus were studied in the ferret tracheal organ culture system. ciliary activity and viral replication were measured. ciliary activity was reduced more rapidly by a/hong kong/45/68 (h3n2) (a/hk) and a/victoria/3/75 (h3n2) (a/vic) than by a/new jersey/8/76 (hsw1n1) (a/nj), a/scotland/840/74(3hn2) (a/scot), or a/ussr/90/77 (h1n1) (a/ussr). a/hk, a/vic, and a/scot produced titers of virus higher than a/ussr or a/nj during the first three days after infection ...1979399387
salicylate intoxication and influenza in ferrets.a model of salicylate intoxication was developed in ferrets to permit the evaluation of the interaction with viruses isolated from patients with reye's syndrome. salicylate intoxication produced a mild elevation of the serum glutamic oxaloacetic transaminase and fatty changes in the liver, but these changes differed from those seen in reye's syndrome on light and electron microscopy. salicylates were associated with decreased activity of hepatic phosphorylase and a slight depression of activity ...1979432001
heterotypic immunity to influenza in ferrets.heterotypic immunity to influenza virus in ferrets operated against heterotypic influenza viruses but not heterologous viruses. contrary to prior reports, the protection conferred lasted for at least 18 months. this type of immunity limited virus shedding but did not prevent infection. these results suggest that this phenomenon could play a role in determining the severity of infections caused by type a influenza viruses in humans.19807216432
[use of monoclonal antibodies for the antigenic analysis of the hemagglutinin of influenza viruses (h3n2) isolated in the ussr in 1979-1980].monoclonal antibodies for the a/england/864/75 strain hemagglutinin were used for antigenic analysis of influenza a (h3n2) viruses isolated in the ussr in december 1979--january 1980. the results of studies with 5 different monoclones were compared with those obtained with postinfection ferret sera. it was shown that several variants of epidemic strain could circulate during one epidemic season. the epidemic in the ussr in december, 1979--january 1980 was caused by influenza viruses h3n2 similar ...19807434736
equine influenza in the netherlands during the winter of 1978-1979; antigenic drift of the a-equi 2 virus.influenza virus a-equi 2(heq2neq2) caused an epizootic in the netherlands in the winter of 1978-1979. horses vaccinated with a/equi/praha/56 (heq1neq1) and a/equi/miami/63 (heq2neq2) were also infected and showed clinical signs. the virus involved showed a marked antigenic drift from the prototype and vaccine strain a/equi/miami/63 (heq2neq2). infection of ferrets with the dutch/79 isolates gave rise to high haemagglutination-inhibition antibody titres to a number of a-equi 2-1963, 1968 and 1979 ...19817245173
differential distribution of virus and histological damage in the lower respiratory tract of ferrets infected with influenza viruses of differing virulence.the distribution of four strains of influenza virus [a/pr/8/34 (h0n1) and clone 64d (attenuated for ferrets) and clones 64c and 7a (virulent for ferrets) of the recombinant virus a/pr/8/34--a/england/939/69 (h3n2)] in the lower respiratory tract (trachea, bronchi and the hilar, intermediate and outer alveolar zones of the lung) of ferrets was monitored daily for 4 days after intranasal inoculation. on day 1, some animals had high virus titres in all the tissues but in other animals virus was und ...19817288401
analysis of antigenic drift in the haemagglutinin molecule of influenza b virus with monoclonal antibodies.antigenic drift in the haemagglutinin (ha) molecule of influenza b viruses was studied with monoclonal antibodies. antigenic drift occurred in each of the 12 different epitopes studied and there was evidence that at least two antigenically distinguishable influenza b virus strains can co-circulate during an epidemic. the frequency of antigenic variation in the ha of influenza a strains. haemagglutination inhibition (hi) tests on antigenic variants selected with 12 different monoclonal antibodies ...19817288409
replication of avian influenza a viruses in mammals.the recent appearance of an avian influenza a virus in seals suggests that viruses are transmitted from birds to mammals in nature. to examine this possibility, avian viruses of different antigenic subtypes were evaluated for their ability to replicate in three mammals-pigs, ferrets, and cats. in each of these mammals, avian strains replicated to high titers in the respiratory tract (10(5) to 10(7) 50% egg infective doses per ml of nasal wash), with peak titers at 2 to 4 days post-inoculation, s ...19817309229
antigenic and genomic analyses of influenza a(h1n1) viruses from different regions of the world, february 1978 to march 1980.antigenic analysis of influenza a(h1n1) virus isolates by hemagglutination inhibition reactions with postinfection ferret sera and mouse monoclonal antibodies showed that, although the predominant virus in 1978 to 1979 had an a/brazil/11/78-like hemagglutinin, several new antigenic variants could be detected which differed from those identified in 1977 to 1978. most of the variants showed very minor changes and did not achieve epidemiological significance. genome analysis by ribonucleic acid-rib ...19816163725
the relation of interferon and nonspecific inhibitors to virus levels in nasal washes of ferrets infected with influenza viruses of differing virulence.two clones (7a, virulent; 64d, attenuated) of a recombinant influenza virus (a/pr/8/34-a/england/939/69 (h3n2)) were inactivated at the same rate by viral inhibitors present in nasal washes taken from both clone 7a- and clone 64d-infected ferrets. both clones induced similar levels of interferon in the nasal washes of infected animals. the onset and rise of interferon production occurred at the same time for both clones, and was associated with a decline in virus titres. in addition, both clones ...19816164382
[new antigenic variants of influenza a(h1n1) virus detected in the ussr in 1979].studies of influenza a (h1n1) viruses isolated in the spring of 1979 in the ussr showed all the 73 strains to belong to influenza a (h1n1) virus but to be heterogeneous. apart from the strains identical with the reference a/ussr/90/77 and a/brazil/11/78 as well as intermediate ones, 14 strains were identified and found to be new drift variants. a composite analysis of representative strains of this group (a/ussr/50/79 and a/ussr/61/79) by hi test with diagnostic rat and ferret sera as well as mo ...19816168112
field and laboratory studies of equine influenza viruses isolated in 1979.experimental ponies developed signs of disease four days after the intranasal instillation of a/england 1/79 equine influenza virus and virus was recovered from the nasopharynx from the second to the ninth day. no significant antigenic difference was found between the virus and the prototype a/miami 1/63 virus, using post infection ferret and chicken sera and post vaccination pony sera. no antigenic differences were found between four viruses isolated between january and july 1979, although some ...19816275599
failure to detect hemagglutination-inhibiting antibodies with intact avian influenza virions.avian influenza viruses replicate in a variety of mammals and birds, yet hemagglutination inhibition tests show that postinfection sera from these animals (e.g., ferrets and ducks) have insignificant levels of antibodies (hinshaw et al., infect. immun. 34:354-361, 1981). this suggested that avian influenza viruses, in contrast to mammalian viruses, may not induce a significant humoral response. studies reported here indicate that avian influenza viruses do induce high levels of antibodies in fer ...19826292104
antigenic properties of some equine influenza viruses.the antigenic relationships between the haemagglutinins of five a/equine-1 viruses and between six a/equine-2 viruses were examined using post-infection ferret and immunized pony sera. similar results were obtained with sera from both species for the a/equine-1 viruses and these confirmed minor antigenic differences between the prototype a/prague 1/56 virus and viruses isolated in england in 1973 and 1977. considerable antigenic differences were found between five of the a/equine-2 viruses, usin ...19826181759
elevation of nasal viral levels by suppression of fever in ferrets infected with influenza viruses of differing virulence.the effect of suppression of fever on viral levels in nasal washes of ferrets infected with either of two clones (7a, virulent; 64d, attenuated) of the recombinant influenza virus a/puerto rico/8/34-a/england/939/69 (h3n2) was studied. the febrile response was reduced by shaving the ferrets or by treating them with sodium salicylate, which had no noticeable effect on the inflammatory response. for both clones, significantly more virus was shed in the nasal washes of ferrets whose febrile respons ...19827069233
antigenic and genetic characterization of a novel hemagglutinin subtype of influenza a viruses from gulls.influenza a virus isolates from ring-billed, franklin, blackback, and herring gulls in the united states possess a hemagglutinin (ha) distinct from the 12 reference ha subtypes. serological assays (hemagglutination inhibition and double-immunodiffusion) with specific antisera to reference strains and to a representative gull isolate showed that the ha of the gull virus was not antigenically related to that of any known subtype. the gull virus did not replicate in ducks or chickens but did replic ...19827097861
anti-influenza a virus activity of amantadine hydrochloride and rimantadine hydrochloride in ferret tracheal ciliated epithelium.the activities and toxicities of amantadine hydrochloride and rimantadine hydrochloride against influenza a/alaska/6/77 (h3n2) and a/bangkok/1/79 (h3n2) viruses were compared in organ cultures and ferret tracheal ciliated epithelium. pretreatment of cultures with concentrations (0.5 and 1 micrograms/ml) comparable to those found in human serum after oral administration of amantadine revealed that rimantadine produced significantly longer protection than amantadine against virus-induced cytopathi ...19827103458
the inadequacy of rectal temperature measurements for assessing the effects of antiviral drugs on influenza virus infection of ferrets.from 6 experiments in which 99 ferrets were infected with influenza virus a/finland/74 and treated with various agents which suppress virus shedding and other parameters of infection, we assessed whether rectal temperature correlated with nasal virus shedding. a number of temperature and virus-shedding related parameters were determined for each experiment but statistical analysis showed little correlation between them, although an elevated temperature occurred at some time after infection. the ...19827161369
analysis of antigenic variation in equine 2 influenza a viruses.influenza outbreaks involving viruses of the h3n8 subtype (equine 2) often occur in vaccinated horses. for this reason, a series of influenza viruses of the h3n8 subtype were examined to determine if antigenic variation could be detected in isolates during the period 1963-81. antigenic analyses with post-infection ferret sera and monoclonal antibodies showed that the haemagglutinins of recent isolates were antigenically distinguishable from the prototype a/eq/miami/1/63 and that antigenically di ...19836601538
the role of naturally-acquired bacterial infection in influenza-related death in neonatal ferrets.concomitant, naturally-acquired bacterial infection was the cause of some deaths occurring in neonatal ferrets infected with the attenuated influenza virus a/puerto rico/8/34, these being prevented by antibiotic therapy. bacterial infection played an insignificant role in the greater number of deaths following inoculation with the virulent clone 7a (of the recombinant influenza virus a/puerto rico/8/34-a/england/939/69/(h3n2]. as seen previously with clone 7a some ferret neonates infected with a ...19836639875
characterization of an influenza a host range mutant.a mixed infection of primary chick kidney cells at 38 degrees with a/ann arbor/6/60 cold adapted virus and a/alaska/6/77 wt virus yielded a cold-reassortant virus, cr43-clone 3, which had a host range different from that of either parent. it does not produce detectable virus when grown in madin-darby canine kidney cells, while growing normally in primary chick kidney cells at 33 degrees. both parents, however, grow well in either cell type at 33 degrees c. genotypic analysis of viral rna electro ...19836649412
[epizootic swine influenza on animal farms in brittany].since 1976, seroepidemiological surveys using radial haemolysis and isolation trials from samples collected from pigs at the abattoir showed that brittany was an important reservoir of swine subclinical infections due to the human influenza a viruses h3n2. influenza a h1sw n1sw subclinical infections sporadically occurred from 1979 to 1981. in january 1982 an epizootic started in finistère which spread from west to east. the h1sw and n1sw antigens of 28 stains isolated from 1979 to 1982 were stu ...19836658105
surveillance of influenza in houston, texas, usa: gradual transition from a/victoria/75 (h3n2) to a/texas/77 (h3n2) predominance and antigenic characterization of "intermediate" strains.influenza epidemics in houston, texas, usa, during the winters of 1975-76, 1976-77, and 1977-78 were attributed to a/victoria/3/75 (h3n2), b/hong kong/5/72, and a/texas/1/77 (h3n2)-like viruses, respectively. both a/victoria and a/texas viruses were detected towards the end of the 1976-77 epidemic and throughout the 1977-78 epidemic. to determine if there had been a gradual transition in the predominant strain, 267 viral isolates from the 1975-76 epidemic were tested for a/texas virus. eight spe ...19836190585
distribution of viral antigen with the lower respiratory tract of ferrets infected with a virulent influenza virus: production and release of virus from corresponding organ cultures.using fluorescent antibody techniques, a semi-quantitative survey has been made of the distribution of influenza virus antigen in the trachea, main bronchi, and three zones (hilar, intermediate and alveolar) of all four lung lobes of ferrets following intranasal inoculation of a virulent clone (7a) of the recombinant influenza virus a/pr/8/34-a/england/939/69 (h3n2). the results confirm the indications from our previous quantitative surveys of infectious virus and histological damage in these ar ...19836338151
anti-influenza a activity of combinations of amantadine and ribavirin in ferret tracheal ciliated epithelium.the anti-influenza a activities of amantadine and ribavirin were investigated separately and in combination. ferret tracheal ciliated epithelium was continuously exposed to the drugs at concentrations (0.25, 0.5, and 1 mg/l) comparable to those found in human serum after oral administration. each drug alone produced a modest delay in a/alaska/6/77 (h3n2) induced cytopathic effect. the combination of drugs synergistically delayed cytopathic effect. at 1 mg/l of each, cytopathic effect was prevent ...19836826488
interference following dual inoculation with influenza a (h3n2) and (h1n1) viruses in ferrets and volunteers.the effects of simultaneous inoculation with two attenuated influenza a viruses was studied in ferrets and volunteers. groups of ferrets were inoculated with an influenza a (h3n2) or (h1n1), virus or a combination of both viruses: the temperature response, serum and local antibody response, and the change in nasal wash protein concentration was determined. the results showed that both viruses were attenuated for ferrets, and that inoculation with both viruses together did not cause clinical reac ...19836834013
the similar interaction of ferret alveolar macrophages with influenza virus strains of differing virulence at normal and pyrexial temperatures.the possibility that ferret lung macrophages may be one factor operating in vivo to prevent infection of susceptible alveolar cells (as demonstrated by organ cultures) by both virulent and attenuated strains of influenza virus has been investigated. phagocytosis of four strains of influenza virus [a/pr/8/34 (h1n1) and clone 64d (attenuated for ferrets) and clones 64c and 7a (virulent for ferrets) of the recombinant virus a/pr/8/34-a/england/939/69 (h3n2)] by ferret alveolar macrophages in vitro ...19836875518
comparison of monoclonal antibodies with ferret sera for the characterization of influenza a (h3n2) virus strains in a computer system.a panel of murine monoclonal antibodies was generated against five different influenza a (h3n2) virus strains, isolated between 1977 and 1980. monoclonal antibodies with defined specificities in haemagglutination inhibition tests for the strains against which they had been raised were selected. eventually 18 of these were chosen and tested against a large number of recent h3n2 isolates. the results were compared with those obtained with antisera from ferrets immunized with the five strains menti ...19846526140
a genetic and monoclonal analysis of high-yielding reassortants of influenza a virus used for human vaccines.this paper describes two methods of analysis using monoclonal antibodies and rna hybridization to characterize variation in the haemagglutinins of seven high-yielding influenza virus reassortants used for inactivated vaccine production. the results show that variants' were selected in producing these genetic reassortants. the haemagglutinins of two reassortants showed both antigenic and structural differences from their wild-type (wt) parents as detected by the two methods of analysis. these var ...19846699022
an investigation of antigenic drift of neuraminidases of influenza a (h1n1) viruses.a newly developed lectin neuraminidase test (lnt) and a panel of mouse monoclonal and post-infection ferret antibodies have been used to analyse antigenic drift in n1 neuraminidases of influenza a viruses isolated between 1933 and 1957 and also between 1977 and 1980. significant antigenic differences were detected among the 'early' (1933-57) viruses since the na of viruses isolated one year apart could be distinguished serologically. the na of the 're-emerged' virus a/ussr/92/77 (h1n1) was antig ...19846707471
differential replication of attenuated and virulent influenza viruses in organ cultures of ferret bronchial epithelium. brief report.in contrast to its abundant replication in ferret nasal epithelium in vivo and in vitro, comparable to that of the virulent strains, the attenuated influenza virus a/pr/8/34 produced much lower yields than the virulent strains in organ cultures of bronchial epithelium agreeing with its relative inability to infect the lower respiratory tract of ferrets. the replication of another attenuated strain showed different temperature characteristics in bronchial epithelium to that in nasal turbinate epi ...19846721679
the intestine of ferret--a possible site of influenza virus replication.anal virus shedding and stimulation of the immune response were observed in ferrets after oral and rectal administration of influenza a/hongkong/1/68 (h3n2) virus. despite of the low ph in the stomach, the virus had reached the intestines after oral administration and was found in high concentration in faeces and in mucosal cells lining the colon. using immunofluorescent staining, the virus antigen was detected in cytoplasm of columnar epithelial cells. virus replication also occurred in the res ...19846148853
antigenic heterogeneity among influenza a(h3n2) field isolates during an outbreak in 1982/83, estimated by methods of numerical taxonomy.fourteen influenza a(h3n2) field isolates, mainly obtained during the first weeks of the 1982/83 influenza epidemic in the netherlands, and nine influenza a(h3n2) reference strains were examined by means of haemagglutination inhibition (hi) tests with 23 polyclonal ferret sera. the resulting hi patterns were subjected to various methods of numerical taxonomy using, among others, taxonomic distance and correlation between strains for resemblance coefficients. marked differences between distance a ...19853973384
analysis of antigenic relationships among influenza virus strains using a taxonomic cluster procedure. comparison of three kinds of antibody preparations.hemagglutination inhibiting (hi) monoclonal antibody preparations (ma) were raised against six influenza a (h3n2) strains from the period 1977-1982. twenty-three hybridomas were selected and titrated in hi assays against these strains and against 18 influenza a (h3n2) viruses isolated in the netherlands during the seasons 1981-1982 and 1982-1983. similar hi tests were performed with conventional post-infection ferret antisera and with ferret antisera adsorbed with heterologous strains of influen ...19853988875
attenuation of wild-type human influenza a virus by acquisition of the pa polymerase and matrix protein genes of influenza a/ann arbor/6/60 cold-adapted donor virus.wild-type influenza a viruses can be attenuated for humans by the acquisition of genes from the a/ann arbor/6/60 cold-adapted (ca) donor virus. six-gene reassortants, that is, viruses containing the hemagglutinin and neuraminidase surface glycoprotein genes of the wild-type virus and the six remaining rna segments of the ca donor virus, are consistently attenuated for humans. during the production of a six-gene reassortant virus containing the surface glycoproteins of the a/washington/897/80 (h3 ...19854056002
[immunovirologic markers of the risk of influenza a h3n2 among swine].a seroepidemiological survey using the radial haemolysis test has been performed on a representative sampling of the pig herds in brittany. since 1978, influenza a h3n2 strains spread in that reservoir giving subclinical infections. we detected antibodies directed against the influenza prototypes isolated during the human outbreaks from 1973 to 1977. only one h3n2 virus was isolated in 1980: its antigenic structure was in agreement with the previous serological data. in 1984 outbreaks of swine i ...19854095329
cold-adapted reassortants of influenza a virus: pathogenicity of a/ann arbor/6/60 x a/alaska/6/77 reassortant viruses in vivo and in vitro.cold-adapted reassortants of a/ann arbor/6/60 x a/alaska/6/77 viruses made in mdck cells have recently been assessed genotypically and for temperature-sensitive and cold-adapted phenotypes. these reassortants were used to infect ferrets and hamsters and to inoculate organ cultures of hamster tracheal rings, in order to assess their degree of virulence. virulence in the three model systems corresponded quite well, and a correlation between loss of virulence and particular a/aa/6/60 genes present ...19863753204
molecular studies of the differential replication at pyrexial temperatures of two influenza viruses differing in virulence for ferrets.replication of a virulent clone (7a) of the reassortant influenza virus a/puerto rico/8/34-a/england/939/69 (h3n2) in ferret nasal turbinate tissue is less affected than that of an attenuated clone (64d) by temperatures which occur during pyrexia in ferrets. this is a factor which contributes to the difference in virulence of the two clones. the differential replication of the two clones at pyrexial temperatures has been reproduced in allantois-on-shell (egg-bit) cultures, and the synthesis of v ...19863765825
use of indirect and competitive elisas to compare isolates of equine influenza a virus.antigenic differences within equine-1 and equine-2 isolates of influenza were studied by haemagglutination inhibition tests, indirect elisa and competition elisa, using the same antisera. better differentiation was obtained with the competition elisa than with the other two tests. all three methods produced similar relationships within the equine-1 isolates but differed in their ability to differentiate the equine-2 isolates where the competition elisa was superior and produced epidemiologically ...19863793836
host cell-mediated variation in h3n2 influenza viruses.the influence of the host cell on the selection of antigenic variants of influenza a h3n2 viruses and the relevance of host cell selection to the induction of immunity by these viruses have been investigated. influenza viruses were isolated from human clinical samples during a single epidemic, were passaged in mammalian madin-darby canine kidney (mdck) cells or in embryonated hens eggs, and were tested for antigenic variability in the hemagglutinin (ha) molecule with a panel of monoclonal antibo ...19873811239
production of passive immunity in neonatal ferrets following maternal vaccination with killed influenza a virus vaccines.neonatal ferrets may be passively immunized following maternal vaccination with formalin-inactivated influenza a virus vaccine, but the level of protection from partial to complete depends upon the number of doses used to vaccinate the mother, the presence or absence of aluminum hydroxide adjuvant, whether or not the mothers were 'primed' by prior infection with a serologically heterologous type a virus, and the age of the neonate at challenge. neonates were completely protected up to 2 weeks of ...19873817868
intestinal replication of influenza a viruses in two mammalian species. brief report.the sites of replication of influenza a viruses in ferrets and pigs were studied. the majority of the swine, equine, and avian influenza a viruses tested were recovered from the intestinal tract of ferrets as well as from the respiratory tract; most of the human influenza viruses studied were recovered only from the respiratory tract. in contrast with ferrets, only hong kong/1/68 (h 3 n 2) influenza virus was recovered from the intestinal tract of pigs. despite the large biological variability f ...19873827601
effect of upper respiratory infection on hearing in the ferret model.in an effort to develop an adult animal model for acquired viral-induced hearing loss, three groups of mature ferrets were inoculated intranasally with respiratory viruses (influenza a/port chalmers, influenza b/mass, and parainfluenza i), which have been implicated as causative agents in idiopathic sudden hearing loss (ishl). all ferrets challenged with influenza a/port chalmers (a/pc) exhibited clinical signs of infection, but neither of the other two groups exhibited such signs. conductive an ...19873039863
sequential infection or immunization of ferrets with a series of influenza a (h3n2) strains (report to the medical research council's sub-committee on influenza vaccines (cdvip/iv)).previous studies of boys at christ's hospital school have indicated that annual immunization with influenza virus vaccines did not significantly reduce the total incidence of influenza infection compared to unimmunized subjects. in view of the implications of this result, a similar study was conducted in ferrets to clarify these findings. groups of ferrets were immunized or infected with a series of influenza a (h3n2) viruses over an 18-month period, and the immunity to subsequent live virus cha ...19873315713
serological studies with influenza a(h1n1) viruses cultivated in eggs or in a canine kidney cell line (mdck).pairs of influenza a(h1n1) viruses cultivated from the same clinical specimen in canine kidney (mdck) cells or in embryonated hens' eggs can frequently be distinguished by their reactions with monoclonal antibodies to haemagglutinin and with antibodies in ferret or human sera. egg-adapted virus, further passaged in mdck cultures remained "egg-like" in serological characteristics indicating that the differences in their serological reactions were not a direct result of host cell-dependent glycosy ...19873496984
bacterial adherence to the upper respiratory tract of ferrets infected with influenza a virus.a ferret model was used to study bacterial adherence in animals with influenza. ferrets were inoculated intranasally with influenza a3/hong kong/1/68 virus. antiviral serum antibodies were apparent by day 5. on days 3, 5, 7, 9, and 11, three virus-inoculated and two uninoculated controls were anesthetized, exsanguinated, and decapitated, and the lower jaw was removed. each animal was inoculated intranasally with a 1-ml suspension containing 20 mg (dry wt) of either 3h-labeled staphylococcus aure ...19873554259
four viral genes independently contribute to attenuation of live influenza a/ann arbor/6/60 (h2n2) cold-adapted reassortant virus vaccines.clinical studies previously demonstrated that live influenza a virus vaccines derived by genetic reassortment from the mating of influenza a/ann arbor/6/60 (h2n2) cold-adapted (ca) donor virus with epidemic wild-type influenza a viruses are reproducibly safe, infectious, immunogenic, and efficacious in the prevention of illness caused by challenge with virulent wild-type virus. these influenza a reassortant virus vaccines also express the ca and temperature sensitivity (ts) phenotypes in vitro, ...19883336068
influenza infection causes airway hyperresponsiveness by decreasing enkephalinase.ferret tracheal segments were infected with human influenza virus a/taiwan/86 (h1n1) in vitro. after 4 days, the smooth muscle contractile responses to acetylcholine and to substance p were measured. the response to substance p was markedly accentuated, with a threefold increase in force of contraction at a substance p concentration of 10(-5) m, the highest concentration tested. in contrast, the response to acetylcholine was not affected by viral infection. histological examination of tissues re ...19883042736
antigenic heterogeneity within influenza a (h3n2) virus strains.on the basis of their antigenic properties, influenza virus strains are classified into types and subtypes, which are further subdivided into variants that differ to various degrees in haemagglutination-inhibition assays. evidence is presented that during infection with an influenza a(h3n2) virus the respiratory tract of a human patient often harbours more than one antigenic virus variant. these variants are frequently propagated by embryonated fowl eggs and monkey cells with different efficienc ...19883260141
in vivo localization of staphylococcus aureus in nasal tissues of healthy and influenza a virus-infected ferrets.an in vivo ferret model was used to study the association of staphylococcus aureus with specific tissues of the nasal cavity in both control and influenza a virus-infected animals. ferrets were inoculated intranasally with various doses of influenza a3/hong kong/1/68 virus. on days 2, 5, 9 and 14, four or five virus-inoculated and two uninoculated controls were challenged intranasally with a 1-ml volume of radiolabeled s. aureus (3 mg dry wt), a clinical isolate of low passage history. ferrets w ...19892542970
origin of the hemagglutinin on a/equine/johannesburg/86 (h3n8): the first known equine influenza outbreak in south africa.a severe influenza outbreak occurred in horses in south africa in 1986. the causative agent was identified as an influenza virus [a/equine/johannesburg/86 (h3n8)]. antigenic analyses of the hemagglutinin (ha) with ferret antisera and monoclonal antibodies showed that the eq/johannesburg/86 virus is similar to recent equine h3 viruses. the nucleotide sequence analysis on the ha genes of eq/johannesburg/86 and other equine h3 influenza viruses, together with the epidemiological data, clearly demon ...19892548457
mechanism of immunity to influenza: maternal and passive neonatal protection following immunization of adult ferrets with a live vaccinia-influenza virus haemagglutinin recombinant but not with recombinants containing other influenza virus proteins.neonatal ferrets are protected against infection with influenza virus by milk-derived anti-influenza virus igg after suckling on an immune mother. live vaccines protect better than killed vaccines despite their stimulation of lower maternal haemagglutination-inhibiting antibody levels. this suggests that antibody to virus proteins other than the haemagglutinin may also be involved. to investigate this, adult ferrets were immunized intradermally with live vaccinia-influenza virus recombinants eac ...19892732721
influenza a (h1n1) vaccine efficacy in animal models is influenced by two amino acid substitutions in the hemagglutinin molecule.the immunogenicity and protective efficacy of formalin-inactivated vaccines prepared from influenza a (h1n1) viruses grown in mdck cells and in eggs was compared in animal models. the a/chr/157/83 virus grown in mdck cells (157m) differed by two amino acid substitutions in the ha molecule from the corresponding virus grown in eggs (157e) and the two viruses could be distinguished antigenically by monoclonal and polyclonal antibodies. following two intramuscular injections of vaccine in ferrets, ...19892741341
laboratory characterization of a swine influenza virus isolated from a fatal case of human influenza.a swine influenza virus-like type a (h1n1) virus, designated a/wisconsin/3523/88, was isolated in september 1988 from a wisconsin woman who had died with primary viral pneumonia. antigenic analyses with hemagglutinin-specific monoclonal antibodies and postinfection ferret serum indicated that the hemagglutinin of a/wisconsin/3523/88 was antigenically closely related to viruses currently circulating in swine. genetic analysis of the a/wisconsin/3523/88 virus by rna fingerprinting and partial rna ...19892754013
assessment of signs of influenza illness in the ferret model.the ferret model of influenza a infection was evaluated to determine whether physical signs of influenza illness in addition to fever could be adequately followed. ferrets were evaluated for nasal and systemic signs of influenza infection in a blinded, randomized protocol. nasal signs were scored depending on the degree of nasal discharge and congestion. systemic signs were evaluated on the basis of the activity level of ferrets. nasal and systemic signs in ferrets challenged with influenza bega ...19892760163
efficacy of inactivated influenza a virus (h3n2) vaccines grown in mammalian cells or embryonated eggs.influenza virus (h3n2) host cell variants isolated from a single infected individual were compared for their protective efficacies when used as formalin-inactivated purified whole virus vaccines in ferrets. a/mem/12/85 virus grown in embryonated chicken eggs (egg-grown), which differs from a/mem/12/85 grown in mammalian madin-darby canine kidney cells (mdck-grown) by a single amino acid substitution in the hemagglutinin molecule, was shown to be distinguishable by immune ferret serum. ferrets we ...19892760480
evaluation of the anti-influenza virus activities of 1,3,4-thiadiazol-2-ylcyanamide (ly217896) and its sodium salt.1,3,4-thiadiazol-2-ylcyanamide (ly217896) and its sodium salt were shown to be effective against influenza a and b viruses in vitro and in the mouse model. in nondividing confluent mdck cells, the 50% inhibitory concentration of ly217896 ranged from 0.37 to 1.19 micrograms/ml against various strains of influenza a virus and from 0.75 to 1.54 micrograms/ml against various strains of influenza b virus, with no apparent cytotoxicity. however, at a concentration of 0.31 microgram/ml, ly217896 inhibi ...19902073106
a 36 nucleotide deletion mutation in the coding region of the ns1 gene of an influenza a virus rna segment 8 specifies a temperature-dependent host range phenotype.previously a spontaneous 36 nucleotide deletion in the coding region of ns1 was detected in the ns gene of a reassortant virus (cr43-3) recovered from a dual infection by the influenza a/ann arbor/6/60 cold-adapted (ca) mutant and wild-type (wt) influenza a/alaska/6/77 (h3n2). the hemagglutinin, neuraminidase and ns genes were derived from the wild type virus parent while the other 5 genes were derived from the ca parent. the cr43-3 reassortant virus exhibited: (i) a host range (hr) phenotype, i ...19902138396
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