Avian Diseases: The Creation and Evolution of P. Philip Levine's Enduring Gift.

This account has two aims. The first is to provide a tribute to Dr. Pincus Philip Levine, the founder of Avian Diseases.

Classification of Marek's disease viruses according to pathotype: philosophy and methodology.

The concept of pathotype in Marek's disease (MD) probably dates from the recognition of a more virulent form of the disease in the late 1950s (Benton & Cover, 1957). Distinctions between MD virus strains were further expanded with the description of the vv pathotype in the early 1980s and of the vv+ pathotype in the 1990s. Pathotype designations reflect important biological properties that correlate with the break-through of vaccinal immunity in the field.

Comparative susceptibility of Marek's disease cell lines to chicken infectious anemia virus.

Chicken infectious anemia virus (CIAV) is known to infect and replicate in various Marek's disease chicken cell lines (MDCCs) derived from Marek's disease (MD) tumors. One line, MDCC-MSB1, has been the substrate used in most studies. We compared a total of 26 MDCCs, including two sublines of MDCC-MSB1, MSB1 (L) and MSB1 (S), four other MD tumor-derived lines, and 20 lines derived from MD virus-induced local lesions, for susceptibility to the Cux-1 and CIA-1 strains of CIAV.

Control of avian encephalomyelitis: a historical account.

Avian encephalomyelitis control methods were not developed until the 1950s although the disease had been discovered and described over 20 yr earlier. Inability to transmit the infection by other than intracerebral inoculation, lack of suitable immunologic methods, the unknowing use of immune chickens or embryos for experimental studies, and reliance on a highly adapted strain of virus rather than fresh field isolates were the main reasons for a general lack of progress. In the absence of supportive experimental data, at least two commercial breeding organizations turned to the use of a crude chicken brain-propagated virus for vaccination of breeder replacement flocks in the 1950s.

Relationship between the immunosuppressive potential and the pathotype of Marek's disease virus isolates.

Isolates of Marek's disease virus (MDV) representing three pathotypes of differing virulence were compared for relative immunosuppressive properties in genetically susceptible P2a-strain and genetically resistant N2a-strain chickens. Criteria of immunosuppression were 1) persistence of early cytolytic infection (i.e.

Interferon modulation of Marek's disease virus genome expression in chicken cell lines.

Lines of chicken lymphoblastoid cells were established from local lesions induced by simultaneous injection of Marek's disease virus and various stimulants of T-cell activation. Lines developed with regular medium had relatively high mean rates of spontaneous expression of viral internal antigen (6.2%).

Stages of Marek's disease virus latency defined by variable sensitivity to interferon modulation of viral antigen expression.

Cytokines in conditioned medium can suppress expression of viral internal antigens (VIA) in lymphocytes latently infected with Marek's disease virus. In the present study, conditioned media produced by spleen cells stimulated with concanavalin A or by mixed-lymphocyte reaction had significantly greater (P < 0.05) VIA-suppressive activity with lymphocytes harvested from birds at 14 days post infection than with those collected at 7 days.

Cytogenetic studies of cell lines derived from Marek's disease virus-induced local lesions.

Cytogenetic analysis of cell lines derived from Marek's disease virus (MDV) induced local lesions was performed to detect the presence of a chromosomal alteration found previously in cell lines derived from MDV-induced visceral tumors. This chromosomal alteration involves an amplified region on the short arm of chromosome 1. Trypsin G-binding was performed on 12 local-lesion cell lines having various T-cell receptor phenotypes.

Pathologic and serologic characterization of a variant of duck hepatitis type I virus.

A duck hepatitis virus (DHV), isolated from ducks on a farm in Virginia in 1963, was shown to be only partially related to DHV type I (DHV-I) in cross-neutralization and in cross-protection tests. The virus, named DHV-Ia, apparently is a serologic variant of DHV-I; both viruses are serologically distinct from DHV type III. Pathologic responses to DHV-Ia were similar to those described for DHV-I infection.

Stable transfection of reticuloendotheliosis virus-transformed lymphoblastoid cell lines.

Lymphoblastoid T cell lines were established by infection of chicken splenocytes with reticuloendotheliosis virus (REV). The target cells first were cultured in interleukin-containing conditioned medium or were stimulated by concanavalin A, or both. Most cell lines were T cells expressing CD3 and one of the T cell receptors, and all cell lines were positive for major histocompatibility complex (MHC) class II antigens.

Gordon Memorial Lecture. Chicken neoplasia--a model for cancer research.

1. The use of animal models has been immensely important for the advancement of our knowledge of the aetiology and pathogenesis of human diseases, including neoplasia. 2.

Two distinct alpha beta T-cell lineages can be distinguished by the differential usage of T-cell receptor V beta gene segments.

Avian T cells can be divided into three subpopulations based on their expression of distinct T-cell receptors (TCR1, TCR2, and TCR3), ontogeny, and tissue distribution. The TCR1 cells appear to be the equivalent of mammalian gamma delta cells, but the derivation of cells expressing TCR2 and TCR3 has been unclear. Here we report that chickens contain two families of TCR beta variable (V) gene segments, V beta 1 and V beta 2.

Proliferation of chicken lymphoblastoid cells after in vitro infection with Marek's disease virus.

Activated, thymus-derived (T) lymphoblasts were exposed to Marek's disease virus and cultivated in attempts to induce in vitro transformation. After 9 to 15 days, colonies or small clusters of proliferating lymphoblasts were observed in cultures from three of a total of 122 attempts. These developed into proliferating cell cultures that resembled conventional Marek's disease (MD) lymphoblastoid cell lines in terms of growth characteristics and morphology.

Genetic susceptibility of chicken macrophages to in vitro infection with infectious laryngotracheitis virus.

Chicken macrophages are susceptible to infection with infectious laryngotracheitis virus (ILTV), the level of infection being dependent, in part, on the genotype of the host cell. Following infection in vitro a greater proportion of macrophages from the ILTV-resistant J1(B113/113) and N1(B114/114) inbred lines of chickens were found to be positive for ILTV antigens, than macrophages from the ILTV-susceptible M1(B15/15) chickens. The proportion of ILTV-positive macrophages was found to be genetically regulated, in part by the chicken major histocompatibility complex (MHC), although alloantisera to class I and class II MHC antigens did not reduce the number of macrophages infected.

Transformation of T-lymphocyte subsets by Marek's disease herpesvirus.

Marek's disease herpesvirus (MDV)-transformed lymphoblastoid tumor cell lines were characterized for the presence of the surface markers. Monoclonal antibodies were used for CD3 (T-cell receptor [TCR] complex), TCR1, TCR2, and TCR3, CD4, CD8, and Ia antigen by indirect fluorescence staining followed by microscopic examination or flow cytometry. The lymphoblastoid cell lines were obtained from tumors from chickens infected with MDV (n = 44) or from local lesions induced by inoculation of allogeneic, MDV-infected chick kidney cells (n = 56).

Effect of reticuloendotheliosis virus and infectious bursal disease virus on Marek's disease herpesvirus latency.

Birds infected with reticuloendotheliosis virus (REV) were exposed to Marek's disease virus (MDV) to determine if the establishment of MDV latency was affected by REV-induced immunosuppression, while other chickens, already latently infected with MDV, were challenged with REV or infectious bursal disease virus (IBDV) to determine if the consequent immunosuppression caused a return to cytolytic infection. Immunosuppression was assessed by in vitro mitogen stimulation assays with spleen cells. Latently MDV-infected cells were free of viral internal antigen(s) (VIA) but could be identified by their ability to produce VIA after in vitro cultivation.

Pathogenesis of Marek's disease virus-induced local lesions. 1. Lesion characterization and cell line establishment.

Subcutaneous (wing-web) or intramuscular inoculation of chickens with allogeneic normal or Marek's disease virus (MDV)-infected chicken kidney cells induced local lesions visible by 3-4 days postinoculation (PI). Lesions were slightly larger (P less than 0.05) in infected than uninfected chickens 5 and 8 days PI.

Cytotoxic T lymphocytes in reticuloendotheliosis virus-infected chickens.

Cytotoxic T lymphocytes were functionally demonstrated in spleen cells from chickens 7 days post inoculation with reticuloendotheliosis virus using a Cr-release assay. Major histocompatibility complex (MHC)-restricted cytotoxicity was demonstrated using effector and target cells from two different strains of chickens of known avian MHC haplotype. Anti-viral specificity was shown and in vivo generation of MHC-restricted cytotoxicity was evaluated.

Immune response versus susceptibility to Marek's disease.

It was hypothesized that the generation of activated T cells through an efficient and rapid immune response during the early pathogenesis of Marek's disease virus (MDV) infection provides a large pool of target cells for transformation. Therefore, the correlation between genetic susceptibility to Marek's disease (MD) and in vitro mitogenic responses of lymphocytes as a measure of cell-mediated immune competence and efficiency was tested. In one series of trials, spleen cells from strains of chickens with differing levels of susceptibility to MD tumors were stimulated with graded doses of Concanavalin A (Con A) or phytohemagglutin (PHA).

Maintenance of Marek's disease herpesvirus latency in vitro by a factor found in conditioned medium.

Chicken spleen cells latently infected with Marek's disease virus were cultured with and without conditioned medium (CM) obtained from concanavalin A-stimulated chicken spleen cell cultures. The expression of viral internal antigen(s) (VIA), which is usually associated with cultivation, was prevented or markedly reduced by the CM. This effect required the continued presence of CM, since its removal after 48 h resulted in the subsequent appearance of VIA.

Effect of immunocompetence on the establishment and maintenance of latency with Marek's disease herpesvirus.

Marek's disease virus (MDV) infections normally have an early cytolytic phase in lymphoid organs at 3 to 6 days post-infection followed by a period of latent infection. Little is known about the mechanisms that govern latency with herpesvirus infections, including Marek's disease (MD). To investigate the importance of immunocompetence for either the establishment or the maintenance of latency in MD, immunosuppressive treatments were applied prior to infection with MDV or after latency was established.

Turkey herpesvirus. VII. The evolution of Marek's disease in chickens vaccinated at one day of age and challenged at different periods of time after vaccination.

The Single Comb White Leghorn, the Cornell S strain chickens vaccinated at one day of age with cell free Herpesvirus of turkey (HVT) 100 and 1000 focus forming-units (FFU) per bird were raised in isolatores. At different periods of time the vaccinated and control chickens were reared together with chickens with clinical symptoms of Marek's disease previously inoculated with JM-Strain of Marek's disease virus (MDV) in a separate isolation room throughout the experiment. The specific protective effect was 84.

Expression of a putative tumor-associated surface antigen on normal versus Marek's disease virus-transformed lymphocytes.

Various avian tumor cell lines and normal spleen cells from 3 genetic strains of specific-pathogen-free (SPF) chickens were examined for expression of Marek's disease (MD) tumor-associated surface antigen (MATSA). Two anti-MATSA monoclonal antibodies (RPH 6 and EB 29) and a rabbit anti-MATSA antiserum were used in indirect fluorescent antibody tests, and cells were examined by fluorescence microscopy and with a fluorescence-activated cell sorter (FACS). Less than 5% MATSA-positive cells were observed in 2 non-MD tumor cell lines (LSCC-RP 9 and RECC-CU 60) with RPH 6, but 7-82% positive cells were observed with EB 29 or the rabbit antiserum.

Papovavirus infection in hand-fed parrots: virus isolation and pathology.

Papovavirus infection was diagnosed in 44 parrots of at least 18 species exclusive of the budgerigar (Melopsittacus undulatus). The birds were 14 days to 4 months old and had been removed from parental care and hand-fed as nestlings. The birds had been unexpectedly found dead after having evidenced no premonitory signs of illness, or they died following a short (12-to-48-hour) period of lassitude and anorexia.