Research training for veterinarians and graduate education in veterinary medical colleges.
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Education, Graduate↗
Biomedical subjects
B C Easterday
Publications and source records attributed to B C Easterday.
Influenza viral infection of swine in the United States 1988-1989.
Swine are an animal reservoir for influenza viruses capable of causing disease in humans. A serological survey in 1988-1989 demonstrates that subtype H1 influenza viruses continue to circulate at high frequency among swine in the north-central U.S.A. (average 51% incidence). Subtype H3 viruses antigenically similar to current human H3 viruses are circulating at low frequency (average 1.1%), particularly in the southeast U.S.A.
Animals↗
Virulent avian influenza A viruses: their effect on avian lymphocytes and macrophages in vivo and in vitro.
To investigate the pathogenesis of virulent avian influenza A viruses, the effect of A/turkey/Ont/7732/66 (H5N9) (Ty/Ont), A/tern/South Africa/1961 (H5N3) (Tern/S.A.) and A/chicken/Pennsylvania/1370/83 (H5N2) (Ck/Penn) on avian lymphoid cell populations was examined in vivo. Previous studies have shown that infection of chickens with Ty/Ont resulted in the extensive destruction of lymphoid tissues. In this study, other virulent avian H5 influenza viruses, Tern/S.A. or Ck/Penn, had little or no effect on lymphoid tissues of infected chickens. Therefore the effect of Ty/Ont on lymphoid tissue is a specific activity of this virus only and not of other virulent avian H5 influenza strains. To examine the role of viral replication in the destruction of lymphocytes, in vitro cultures of avian macrophages and lymphocytes were inoculated with Ty/Ont. Macrophages supported the synthesis of viral proteins whereas lymphocytes produced small, but detectable amounts of viral protein; however, infectious virus was not produced by either cell type. Furthermore inoculation of chicken spleen cells with Ty/Ont in vivo and in vitro had a profound effect on the proliferative response of lymphocytes to concanavalin A. These results suggest that Ty/Ont infects macrophages as well as lymphocytes in the chicken, and the effects of the virus on both cell types may well contribute to lymphoid necrosis.
Animals↗
Antigenic conservation of H1N1 swine influenza viruses.
Influenza viruses of the H1N1 subtype have been continually circulating in pigs in the U.S.A. for at least 50 years. To examine the level of antigenic variation in these swine viruses, a panel of 60 monoclonal antibodies (MAbs) to the haemagglutinin (HA) of recent swine isolates was prepared. Evaluation of neutralization escape mutants selected with these MAbs defined four antigenic sites on the HA, two of which overlap. Swine viruses isolated over 24 years in an enzootic area in Wisconsin were examined by ELISA and haemagglutination inhibition (HI) with these MAbs and the results indicated that the antigenic sites defined by these MAbs were highly conserved in these viruses. In comparing recent H1N1 viruses from pigs, turkeys, ducks and humans, changes in the antigenic sites were detected on the basis of HI reactivity. However, results of ELISA with these viruses clearly showed that the antigenic sites were still present on almost all H1N1 viruses of swine origin; thus, altered reactivity of these viruses in HI tests with MAbs was not a reflection of changes in the antigenic sites defined by the MAbs. It seems likely that the variation detected in these viruses occurs by a mechanism other than immune selection.
Animals↗
Destruction of lymphocytes by a virulent avian influenza A virus.
Infection of chickens by a virulent avian influenza A virus, A/turkey/Ont/7732/66 (H5N9), was associated with a severe lymphopenia. High titres of infectious virus were found in lymphoid tissues early in infection and were accompanied by severe damage to the lymphocyte populations as demonstrated by histopathological examination. Non-lymphoid cell populations in these tissues were unaffected, as were other organs examined. The viral nucleoprotein was localized by immunoperoxidase staining to lymphocytes in affected tissues early in infection.
Animals↗
Neutralizing epitopes of the H5 hemagglutinin from a virulent avian influenza virus and their relationship to pathogenicity.
To define and characterize the major neutralizing epitopes of the H5 hemagglutinin, a panel of monoclonal antibodies specific for the H5 hemagglutinin of the virulent avian influenza virus A/Turkey/Ontario/7732/66 (H5N9) was prepared. Antibodies which neutralized infectivity of the virus were used to select a panel of escape mutants. Reactivity patterns of the panel of monoclonal antibodies against the panel of mutants by both enzyme-linked immunosorbent assay serology and hemagglutination inhibition operationally defined five distinct epitopes on the H5 molecule. The mutants were analyzed in vivo for virulence in chickens, and the findings indicate that viruses with mutations in four of five epitopes were no less virulent than the wild type, producing a rapidly fatal disease, while all viruses with mutations in the fifth epitope (group 1 mutants) were attenuated. These group 1 mutants were unaltered in the cleavage properties of the hemagglutinin, suggesting that the mechanism of attenuation is unrelated to processing of the hemagglutinin. One of the group 1 mutants, 77B1v, was characterized for its ability to produce necrosis of the spleen and was found to produce none of the lesions in the spleen which are characteristic of the wild-type virus, although virus was present in this organ. The results suggest an altered tissue tropism, perhaps sparing a population of cells critical to an effective immune response.
Animals↗
Pathological lesions in the lungs of ducks infected with influenza A viruses.
To determine histopathological damage in the respiratory tract, ducks were inoculated with five different influenza A viruses, including viruses virulent for other avian hosts. Lungs were collected for detection of virus and histopathological examination. Small amounts of infectious virus were recovered from lungs, and viral antigens were demonstrated by immunoperoxidase staining with monoclonal antibodies to the viral nucleoprotein. Although clinical signs were not detected, lungs of ducks infected with both virulent and avirulent viruses had mild pneumonia characterized by infiltrates of lymphocytes and macrophages. These findings show that although clinical signs are not evident, ducks may have damage to the respiratory tract during influenza.
Animals↗
Antigenic and phenotypic variants of a virulent avian influenza virus selected during replication in ducks.
To evaluate the replication of a highly virulent avian influenza A virus in a potential reservoir host, mallard ducks (Anas platyrhynchos) were inoculated with the virulent strain A/Ty/Ont/7732/66 (H5N9). Viruses recovered from the ducks were analyzed by hemagglutination inhibition (HI) and enzyme-linked immunosorbent assay (ELISA) and found to possess antigenically altered viral hemagglutinins. Plaque formation on the Madin-Darby Canine Kidney (MDCK) cell line and on primary chicken embryo cells was investigated, and isolates recovered from the ducks differed from the wild type by being unable to form plaques on MDCK cells without trypsin. This phenotype did not appear to be due to inefficient cleavage of the hemagglutinin by host cell proteases since hemagglutinin immunoprecipitated from cell lysates was cleaved. Although the plaquing phenotype suggested attenuation of the isolates from the ducks, they were not significantly altered in their virulence for chickens shown by infectivity studies in vivo. These results indicate that replication of influenza A/Ty/Ont/7732/66 virus in ducks can produce antigenic and phenotypic variants which are still highly virulent for domestic poultry.
Animals↗
Evolution to predominance of swine influenza virus hemagglutinin mutants of predictable phenotype during single infections of the natural host.
L and H2 mutants of the A/NJ/11/76 H1N1 strain of swine influenza virus differ by having either a lysine or a glutamic acid at position 153 of the hemagglutinin glycoprotein of the virus. In two separate experiments, experimental infection of swine with various doses of the H2 mutant resulted in the emergence in 11 of 20 animals of virus with the L phenotype. All evidence indicates that the H2----L mutation, selection, and evolution to predominance occurred within the 7-day span of individual infections. L and H2 mutations appear to act as alleles in the adaptation of virus, respectively, to natural and laboratory hosts. Although the gradual evolution of mutants during sequential infections is commonplace, the present recognition of rapid and predictable evolution of mutants of increased replication efficiency and specific phenotype in the natural host, to our knowledge, is unprecedented.
Animals↗
Vaccination of swine with thymidine kinase-deficient mutants of pseudorabies virus.
A mutant of pseudorabies virus (PRV) deficient in thymidine kinase (TK-) activity was isolated and characterized. The mutant grew well in cell culture and did not revert to the thymidine kinase-positive phenotype. The PRV-TK- was not virulent when inoculated intranasally into 3-to 4-week-old pigs and could not be reactivated from the ganglia of these pigs by explantation and cocultivation with susceptible cells several weeks after virus inoculation. Pigs that had been exposed to PRV-TK- were immune to challenge exposure with a virulent strain of PRV. Furthermore, the challenge virus was not recovered from the ganglia of most of these pigs, indicating that colonization of the ganglia by a super-infecting virulent PRV strain was considerably reduced by vaccination.
Animals↗
Antigenic comparisons of swine-influenza-like H1N1 isolates from pigs, birds and humans: an international collaborative study.
The objective of this international collaborative study was to compare recent swine isolates of influenza viruses and determine whether significant antigenic differences among isolates from different areas of the world could be detected. H1N1 viruses isolated from pigs, birds and humans in 12 different countries were compared in haemagglutination-inhibition assays with post-infection ferret sera and monoclonal antibodies to H1N1 strains. Using A/NJ/8/76 as the reference strain, we found that recent swine isolates from Hong Kong, Italy, Japan, and the USA possess a haemagglutinin virtually indistinguishable from that of viruses typically associated with pigs, i.e., A/NJ/8/76. In contrast, recent swine isolates from several European countries (Belgium, Denmark, France, Federal Republic of Germany, and Spain) were distinguishable from A/NJ/8/76, as demonstrated by tests in the various laboratories. These studies suggest that the H1N1 viruses in pigs are antigenically heterogeneous and that the circulation of particular variants is associated with the geographical location of the animals. These results raise the question of whether these viruses originated from the same source, i.e., pigs, and have undergone antigenic drift or, alternatively, were introduced from other hosts, such as birds.
Animals↗
Characterization of bovine herpesvirus-1 isolated from trigeminal ganglia of clinically healthy cattle.
Isolates of bovine herpesvirus-1 (BHV-1) recovered from tissue explants of trigeminal ganglia of clinically healthy cattle were studied in vitro and in an animal model, and their characteristics were compared with those of vaccine and field strains of BHV-1. The isolates could be distinguished by their plaque size on cell monolayers, but were not significantly different in their thermal inactivation profiles at 48 C. Temperature-sensitive mutants were not found among the isolates when they were grown at 41 C. Selected isolates had different pathogenicity when inoculated in young rabbits.
Adrenal Glands↗
Experimental latent and recrudescent bovine herpesvirus-1 infections in calves.
Latent bovine herpesvirus-1 (BHV-1) infection was established in 6 calves and was demonstrated by reinduction of virus shedding after administration of corticosteroids. Latently infected calves failed to transmit BHV-1 during 4 weeks' contact with sentinel calves. Infected calves were killed and necropsied during latency or induced recrudescence. The BHV-1 DNA was demonstrated intranuclearly in trigeminal ganglion neurons by in situ hybridization. The BHV-1 antigen was demonstrated by immunofluorescence in trigeminal ganglion neurons during recrudescence. By electron microscopy, changes in the appearance of the Nissl bodies and a high frequency of nuclear bodies were observed in trigeminal ganglion neurons.
Animals↗
Papillomatosis of the bovine teat (mammary papilla).
A 4th of 667 cattle examined at a Wisconsin abattoir had teat papillomas. Excised teat papillomas were sorted by gross morphologic characteristics into 3 groups: (i) atypical filiform, (ii) atypical flat, and (iii) typical fibropapilloma. Bovine papilloma virus capsid antigen was detected in thin-section slides of the 3 groups of teat papillomas by peroxidase-antiperoxidase assay. The bovine papilloma virus involved with the atypical papillomas could not be characterized by molecular hybridization, because enough pure virus could not be harvested. Homogenates of the 3 groups of teat papillomas were inoculated on 2 ponies and 4 calves. Typical fibropapillomas were produced on the 4 calves, and fibromas, on the 2 ponies. Atypical papillomas were produced only in 2 heifers.
Abattoirs↗
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, similar to the pattern of human and other mammalian viruses in these animals. Most avian strains were recovered for 5 to 9 days post-inoculation. One avian H1N1 virus initially replicated poorly in pigs, but was adapted to this host and even transmitted to other pigs. Replication of the avian viruses occurred in the respiratory tracts of mammals, whereas, in birds, they replicate in the intestinal tract as well. The infected mammals had no significant disease signs and produced low levels of humoral antibodies; however, challenge experiments in ferrets indicated that they were immune. These studies suggest that influenza A viruses currently circulating in avian species represent a source of viruses capable of infecting mammals, thereby contributing to the influenza A antigenic pool from which new pandemic strains may originate.
Adaptation, Physiological↗
Further studies of naturally occurring latent bovine herpesvirus infection.
Attempts were made to enhance the isolation rate of latent bovine herpesviruses from trigeminal ganglia by using a fibroblastic fetal bovine kidney cell line, in addition to Madin-Darby bovine kidney cells, and by superinfecting with a temperature-sensitive helper strain of bovine herpesvirus-1 (BHV-1). Four isolates of latent BHV-1 were obtained from 44 pairs of trigeminal ganglia--thus reflecting no increase in isolation rate over that previously observed. Two isolates of a latent bovine herpesvirus-3 strain DN599 were also obtained. Analysis of plaque morphology of BHV-1 isolates obtained in this and a previous study indicated that several biologically heterogeneous strains were capable of establishing latent infections.
Animals↗
Animals in the influenza world.
In the history of influenza there are many references, notes and comments about influenza epizootics occurring among various non-human animals, sometimes coinciding with epidemics of influenza in human beings. That the first influenza viruses were recovered from non-human animals is not so surprising, given the current knowledge of the distribution of influenza among animals. Influenza viruses are found in a wide variety of mammalian and avian species. In some species the disease that occurs as a result of the infection mimics the influenza disease of human beings, in other species there are no signs of disease, and in others there is disease specific to a species. It is clear that influenza viruses have a significant impact on the health of several animal species. In recent times it has also become clear that many species of animals are inextricably entwined in the puzzle of influenza viruses and human influenza. Our knowledge in animals has provided both questions and answers about the influenza viruses and their diseases. Certainly our understanding of human influenza has been advanced because of the animals in the influenza world.
Animals↗
The epidemiology and ecology of swine influenza as a zoonotic disease.
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Animals↗