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Biomedical subjects

R L Witter

Publications and source records attributed to R L Witter.

At least 55 records · Page 3Linked to original sources
PubMed1983

Monoclonal antibodies with specificity for three different serotypes of Marek's disease viruses in chickens.

A total of 50 antibody-secreting hybridoma cells against Marek's disease virus (MDV) and turkey herpesvirus (HVT) have been produced. Eleven hybridomas were used for serotyping a panel of 15 pathogenic and nonpathogenic strains of MDV and HVT, representing three serotypes. The antibodies from the culture medium have fluorescence antibody (FA) titers of up to 100 and those from mouse ascitic fluid have titers ranging from 10(4) to 10(6). Monoclonal antibody T81 is type-common, i.e., it reacts at equal titer with all MDV and HVT tested. Of the remaining 10 antibodies, eight react only with pathogenic and attenuated strains of MDV (presumably serotype 1), one reacts only with nonpathogenic MDV (presumably) serotype 2), and one reacts only with strains of HVT (presumably serotype 3). Two hybridomas belong to IgG2a and IgG2b subclasses, respectively, and the remaining nine belong to IgG1 subclass. None of the antibodies specific for MDV strains reacted with homologous viruses in serum neutralization (SN), agar gel precipitin (AGP), or membrane immunofluorescence tests. Antibody L78, which is specific for HVT, was reactive with its homologous virus in the SN test; antibody from the culture medium showed an SN titer of 10 and that from mouse ascites a titer of 10,000. None of the antibodies specific for MDV or HVT reacted with other avian or mammalian herpesviruses, avian leukosis viruses (ALV), reticuloendotheliosis viruses (REV), or Marek's disease tumor-associated surface antigen (MATSA) expressed in a lymphoblastoid cell line, MDCC-MSB-1.

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PubMed1982

An IgM-producing B lymphoblastoid cell line established from lymphomas induced by a non-defective reticuloendotheliosis virus.

Chick syncytial virus (CSV), a strain of avian reticuloendotheliosis virus (REV) causes lymphoid tumours in chickens after a prolonged incubation period. A number of CSV-induced tumours were examined for cell surface antigen and were found to be of the B cell type and to produce immunoglobulin. Attempts were made to grow in vitro cell lines from CSV-induced tumours and a lymphoblastoid cell line was established from a liver tumour of a chicken that was inoculated with CSV via the yolk sac in embryo. The donor chicken was viraemic at the time the tumour was removed. The cell line is designated RECC-RP13, it produces non-defective REV, is a B cell type and it produces IgM. It is free from infection with endogenous and exogenous avian leukosis virus (ALV) and has an increased number of chromosomes. Sequences specific to REV were detected in at least four sites in cellular DNA from RECC-RP13. Sequences specific to ALV DNA, beyond that normally found in 151(5) X 7(1) cells, were not found in DNA from this cell line.

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PubMed1982

Tests of association of lymphocyte alloantigen genotypes with resistance to viral oncogenesis in chickens. 1. Marek's disease in F7 progeny derived from 6(3) X 15(1) crosses.

Marek's disease (MD)-susceptible progeny of the B5B5 genotype from the F7 generation derived from crosses of Regional Poultry Research Laboratory inbred lines 6(3) and 15(1) were tested for variation in MD resistance associated with the T lymphocyte antigen loci Ly-4 and Th-1. The four double homozygous genotypic classes of Ly-4 and Th-1 were tested in a 2 X 2 design. The Ly-4bb/Th-1aa chickens were significantly more resistant to MD oncogenesis than the other three genotypes. Thus, resistance within B5B5 genotypes appears to be associated with genetic interaction between two T cell antigen loci, which are not linked with the B complex.

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PubMed1982

Marek's disease in turkeys: lack of protection by vaccination.

Herpesvirus of turkeys, a highly effective vaccine against Marek's disease (MD) in chickens, was ineffective in protecting turkeys against MD. Another tissue-culture attenuated vaccine virus also protected chickens, but not turkeys, from MD. Intact and immunosuppressed turkey poults inoculated with herpesvirus of turkey developed a persistent viremia, but did not have detectable gross or microscopic lesions.

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PubMed1981

B-haplotype influence on Marek's disease, Rous sarcoma, and lymphoid leukosis virus-induced tumors in chickens.

Experiments were conducted to establish whether B-haplotype genes that determine resistance to RSV-induced tumors would also influence resistance to Marek's disease and lymphoid leukosis. Matings of line 6(3) x 15(1) F3 or F4 breeders segregating for the Ea-B locus antigens that are markers for B2 and B5 haplotypes of the B major histocompatibility complex were made to produce B2B2, B2B5, and B5B5 chicks. The chicks were infected with a standard inoculum of one of the three tumor viruses in separate experiments. The B2 haplotype from 6(3) conveyed greater resistance to tumors induced by all three viruses than the B5 from 15(1) chickens. This finding suggests that some gene(s) in the B-haplotype may determine a general ability to resist tumor formation or cause tumor regression.

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PubMed1980

Effect of neonatal thymectomy on pathogenesis of herpesvirus of turkeys in chickens.

Effect of immunosuppression on pathogenicity of herpesvirus of turkeys (HVT) in chickens was studied. In three experiments, newly hatched chickens of two genetic strains were surgically thymectmized and gamma-irradiated and then exposed to HVT. Lymphoid cells of thymectomized-irradiated chickens had reduced in vitro mitogenic response; this result indicated that the immunosuppressive regimen caused suppression of T cell function. The immunosuppressed chickens had more circulating HVT and had a slightly higher frequency of microsocpic lesions in peripheral nerves than the intact control chickens, although the intensity of lymphoproliferation remained very mild and no gross lesions or clinical disease was noted during the 5-week observation period. The absence of significant lesion development in an immunosuppressed host indicated that pathogenic potentials of HVT may be limited.

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PubMed1979

Lymphomas resembling lymphoid leukosis in chickens inoculated with reticuloendotheliosis virus.

Chickens inoculated as embyros or at hatching with the chick syncytial strain of reticuloendotheliosis virus developed a high incidence of lymphoid neoplasms between the 17th and 43rd weeks of age, involving principally the liver and bursa of Fabricius. On the basis of organ distribution, latent period, pathology and surface IgM production, the lymphomas closely resembled those of lymphoid leukosis. One inoculated chicken developed a myxosarcoma. No tumors were observed in uninoculated controls. The tumor-bearing chickens were free of infection with Marek's disease virus and exogenous avian leukosis virus (ALV) of subgroups A, B, C or D. However, the chickens were known to express endogenous ALV genes to varying degrees.

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PubMed1979

Depression of vaccinal immunity to Marek's disease by infection with reticuloendotheliosis virus.

The effect of infection with low-virulence, tissue culture-propagated strains of reticuloendotheliosis virus (REV) on protective vaccinal immunity against Marek's disease (MD) lymphomas was investigated. Vaccinated chickens inoculated at hatching with greater than 10(4) focus-forming units of REV and challenged with MD virus were poorly protected against MD lesion development as indicated by protective indices of 53 to 79% for strain CS (P less than 0.05) and 42 to 49% for strain T (P less than 0.01) compared to 78 to 100% for REV-free controls. Furthermore, the response of blood lymphocytes to mitogen stimulation and the antibody response to sheep erythrocytes and Brucella abortus were less in REV-inoculated chickens than in controls. The REV-induced depression of immune responses was more severe in chickens infected with mildly pathogenic strain T than in chickens infected with the apathogenic strain CS and was generally transient with both virus strains. Little or no depression of immune responses was observed in chickens inoculated with less than 10(3) focus-forming units of REV. These studies extend knowledge on the immunodepressive ability of low-virulence REV strains and establish that infection with these viruses depresses certain parameters of MD vaccinal immunity, an important model for cellular immunity against virus-induced neoplasia in the chicken.

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PubMed1979

Lymphoid neoplasms in chicken flocks free of infection with exogenous avian tumor viruses.

More than 4,500 breeding female chickens of nine inbred lines maintained under specific-pathogen-free conditions to approximately 500 days of age were studied. Routine monitoring and special assays indicated that they were free of infection by exogenous viruses of the leukosis-sarcoma and the reticuloendotheliosis groups. Some birds were maintained free of Marek's disease (MD) virus infection in plastic isolators, and others were maintained in conventional chicken houses and vaccinated with the herpesvirus of turkeys to prevent the lesions of MD. Ten birds bearing lymphoid tumors were observed in two sublines of one line of chickens known to produce embryos that spontaneously produce Rous-associated virus, type 0 (RAV-O), an endogenous virus of the chicken. Four tumors were found in chickens of one subline maintained free of MD virus infection in isolators. These tumors did not involve the bursa and had some histologic features different from those typical of lymphoid leukosis. Six tumors were found in chickens of the other subline that were vaccinated to prevent MD; these tumors involved the bursa and were typical of lymphoid leukosis but not MD. These results suggest that two types of tumors may have been observed. The fact that DNA extracted from both types of tumors did not contain exogenous lymphoid leukosis virus sequences confirms the virologic evidence that exogenous viruses were not involved. The fact that endogenous viral sequences were not increased in copy number suggests that the endogenous virus RAV-O did not directly induce the tumors. Two birds with tumors not involving the bursa were found alive, and transplantable lymphoid tumors were developed. These tumors were of T-cell origin rather than of bursa cell origin as would be expected of lymphoid leukosis. These are the first reported lymphoid tumors that have been observed in the absence of known exogenous tumor virus infection in chickens. Our evidence suggests that the endogenous virus RAV-O did not play a primary role in the induction of these tumors.

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PubMed1978

A phosphonoacetate-resistant mutant of herpesvirus of turkeys.

A phosphonoacetate (PA)-resistant mutant of the herpesvirus of turkeys (HVT) was isolated and characterized. The mutant of HVT resistant to PA (HVTpa) replicated in duck embryo fibroblast (DEF) culture in media containing 300 microgram PA/ml, whereas the replication of the wild type of HVT (HVTwt) was completely inhibited in DEF culture in media containing 100 microgram PA/ml. The HVTpa was distinct from the HVTwt in plaque morphology, but was indistinguishable antigenically and showed in vitro temperature sensitivity at 41 degrees C (3741 degrees C efficiency of replication was about 5). It replicated poorly in chickens and failed to provide complete protection against challenge with Marek's disease virus (MDV). The HVTpa-induced DNA polymerase had an apparent inhibition constant for PA, an apparent inhibition constant for pyrophosphate, and an apparent Michaells constant for dCTP about 10, 2, and 2.5 times, respectively, greater than the constants for the HVTwt-induced enzyme and was also more thermolabile.

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PubMed1978

Development of cell-mediated immunity to Marek's disease tumor cells in chickens inoculated with Marek's disease vaccines.

Chickens inoculated with herpesvirus of turkeys or with apathogenic or attenuated vaccine strains of Marek's disease virus (MDV) developed a T-cell-mediated immune response to Marek's disease (MD) tumor cells. This immune response was detected in a 4-hour 51Cr-release assay in which effector cells obtained from spleens of vaccinated chickens were reacted with 51Cr-labeled target cells of an MD lymphoblastoid cell line (MSB-1). The cytotoxic effector cells generated by the vaccine viruses had characteristics similar to those noted previously for anti-MSB-1 effector cells generated by MDV. The immune response was specific to MSB-1 cells, because another target cell line (TLT) antigenically unrelated to MSB-1 cells was not lysed by the effector cells nor did the unrelated target cells inhibit the cytotoxicity of effector cells against MSB-1 target in a cold-target inhibition assay. Because MSB-1 cells contain MD tumor-associated surface antigen, we postulated that the immune response detected in the vaccinated chickens may be directed against this antigen and that the antitumor antigen immunity may play a role in the mechanism of vaccine protection against lymphoma development by pathogenic MDV.

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PubMed1978

Suppression and enhancement of mitogen response in chickens infected with Marek's disease virus and the herpesvirus of turkeys.

The kinetics of phytohemagglutinin (PHA) response of peripheral blood lymphocytes from chickens infected with oncogenic Marek's disease (MD) virus (MDV) or nononcogenic herpesvirus of turkeys (HVT) was studied with a whole blood microassay. At about 7 days after inoculation, a depression in PHA response was observed in MDV-inoculated resistant line N or susceptible line 7(2) chickens and in HVT-inoculated line 7(2) chickens. All chickens initially regained their PHA responsiveness. Susceptible chickens that died of MD or developed MD lymphoma in later stages of virus infection showed a second severe depression in PHA response. No depression was observed in HVT-vaccinated chickens when challenged with MDV. The PHA response of MDV-inoculated chickens that survived MD, HVT-inoculated chickens, and HVT-vaccinated MDV-challenged chickens showed evidence of enhancement. The depression of PHA response was studied and was attributed to the suppressive effect of macrophages on T-cell response, a finding consistent with our previous studies on MDV suppression of PHA response.

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PubMed1978

Altered biological and biochemical properties of a phosphonoacetate-resistant mutant of herpesvirus of turkeys.

A phosphonoacetate (PA)-resistant mutant of the herpesvirus of turkeys (HVT) was isolated and characterized. The mutant (HVTpa) replicates in growth medium containing 300 microgram/ml of PA and shows in vitro temperature sensitivity at 41 degrees C (its 37 degrees C/41 degrees C efficiency of replication is about 5). HVTpa replicates poorly in chickens and fails to provide complete protection against MDV challenge. The HVTpa-induced DNA polymerase has an apparent inhibition constant for PA 10 times as great, an apparent inhibition constant for pyrophosphate, twice as great, and an apparent Michaelis constant for dCTP 2.5 times as great as the respective figures for the HVTwt-induced enzyme. The HVTpa-induced enzyme is also more thermolabile.

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PubMed1978

Non-protective variants of Marek's disease vaccine viruses.

Two variant Marek's disease-vaccine viruses failed to induce protective immune responses in chickens and replicated poorly in vivo. One of these, MDV/200D, was defective for growth at 41 degrees C, and clones from this stock had 38 degrees C/41 degrees C plating ratios as high as 10(4). The basis for the poor in vivo replicative ability was not determined.

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PubMed1978

Suppression of mitogen-induced proliferation of normal spleen cells by macrophages from chickens inoculated with Marek's disease virus.

Spleen cells from chickens 7 days after inoculation with Marek's disease virus (MDV) responded poorly to stimulation by phytohemagglutinin (PHA). Addition of these cells to syngeneic normal spleen cells caused of marked suppression of the PHA response of the normal cells. The MDV spleen cells also inhibited the DNA synthesis of MSB-1 lymphoblastoid cells in vitro. The suppressive activity is attributed to the presence in MDV spleen cells of a population of suppressor cells with characteristics typical of macrophages. The suppressor cell activity was not removable by treatment with anti-T or anti-B serum with C, but it was reversible by treatment with carrageenan or carbonyl iron/magnet, by passage through glass wool column, and by adherence to plastic Petri dishes. The adherent MDV spleen cells also showed strong suppressor cell activity against syngeneic normal spleen cells.

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