Kyoung-Oh Cho

Anti-viral and anti-tumor effects induced by an attenuated Marek’s disease virus in CD4- or CD8-deficient chickens

Summary. By vaccination with an attenuated Marek’s disease virus (MDV), strain CVI988, chickens are protected from the development of T cell lymphoma caused by an oncogenic MDV. To clarify the role of T lymphocyte subsets in the protection mechanisms of this vaccine, vaccinated chickens were depleted of T cell subsets by neonatal thymectomy and injections of monoclonal antibodies specific to chicken CD4 and CD8 molecules, and then challenged with an oncogenic MDV, strain Md5. The MDV titers rescued from CD8+ T cells, which are the main targets for latent infection and subsequent transformation by MDV, was much higher in the CD8-deficient vaccinated chickens than in untreated vaccinated chickens at the early stage of the latent phase. However, the neonatal vaccination prevented lymphoma formation by strain Md5 even in either CD4+ or CD8+ T cell-depleted chickens. These results suggest that specific CD8+ T cell responses induced by the MD vaccine play a crucial role in the prevention of MDV infection during the latent phase, but may not be essential for the prevention of lymphoma formation by an oncogenic MDV.

Central nervous system lesions induced experimentally by a very virulent strain of Marek's disease virus in Marek's disease‐resistant chickens

The histological lesions of central nervous system (CNS) in Mareks disease-resistant chickens inoculated with a very virulent Mareks disease virus strain (vvMDV), Md/5, were examined. This vvMDV induced high incidences of CNS lesions as well as visceral and peripheral nerve lesions. The principal histopatho-logical changes of CNS consisted of non-suppurative meningoencephalomyelitis and lymphomatous lesion, which were categorized into two types, non-necrotizing and necrotizing. The main changes in the former type were perivascular cuffing of lymphoid cells of variable thickness. Although diffuse lymphomatous lesions were sometimes observed, gliosis, neuronal and axonal degeneration, and satellitosis as well as demyelination in the myelinated fibre paths, were infrequent. The most significant change of the latter type was necrotizing lymphomatous and, sometimes, non-suppurative inflammatory lesions (malacia). In the malacic foci, all the cells, including infiltrating lymphoid cells, neurons and glial cells, were necrotic or degenerated. The malacic lesions were frequently accompanied by fibrinoid necrosis of blood vessels. The present results indicate that necrotizing vasculitis associated with vvMDV may lead to ischaemic damage which in turn induces necrotizing lymphomatous and sometimes, meningoencephalomyelitis lesions. In addition, it is considered that vvMDV can induce a high incidence not only of CNS lesions, but also of visceral and nerve lesions in Mareks disease-resistant chickens.

Analysis of transcriptional and translational activities of Marek's disease (MD) virus genes in MD central nervous system lesions in chickens

The expression of Mareks disease virus (MDV) gene products and transcripts was observed in tissues obtained from the central nervous system (CNS) of chickens experimentally infected with a very virulent strain (Md/5) of MDV. Many cells antigen-positive for MDV early gene products, but not for late gene products, were detected immunohistochemically in the necrotizing lymphomatous lesions. The positive signals were found only in necrotic or degenerated neoplastic lymphoblasts. Abundant transcriptional activity of MDV genes was observed in the necrotizing lymphomatous lesions for immediate-early and early genes, but not for late ones, by the reverse-transcription polymerase chain reaction. In the non-necrotizing lymphomatous lesions, as well as non-suppurative ones, there were no or very few antigen-positive lymphoblasts for early and late genes, and little transcriptional activity of MDV genes. The necrotizing lesions of the lymphoma were associated with necrotizing vasculitis in which endothelial cells exhibited up-regulation of MHC class II antigen but no viral antigens. The present results indicate that only necrotizing lymphomatous lesions revealed abundant incomplete cytolytic cycle in MDV latently infected neoplastic lymphoblasts.

Significance of Marek's disease virus serotype 1‐specific phosphorylated proteins in Marek's disease skin lesions

Skin tissues were obtained from 12 chickens showing Mareks disease (MD) skin tumour induced by a very virulent MD/5 strain of Mareks disease virus serotype 1 (MDVl) and taken from 24 field broiler chickens (8 to 9-weeks-old) manifesting MD skin tumour. They were examined by the immunohistochemical method in order to examine the topographic expression of MDV1-specific phosphorylated proteins (PP) and by the reverse-transcription polymerase chain reaction following Southern hybridization to analyse their gene transcriptional activity. PP were massively detected and their gene transcripts were abundantly expressed only in the necrotic areas of some experimentally-induced MD cutaneous lymphoma lesions. Strong PP-positive cells were degenerate or necrotic lymphoblasts. The other field or experimentally-induced MD cutaneous lymphoma lesions, even those consisting almost completely of tumorous lymphoblasts, had only a few PP-positive lymphoid cells and few gene transcripts. Necrotic areas of feather pulp MD lymphoma lesions consisting mainly of degenerate or necrotic lymphoblasts and cytolytic feather follicle epithelium (FFE) were also strongly positive for PP. PPs and their gene transcripts were detectable only in the cytolytically infected cells such as FFE and tumorous lymphoblasts converting to the abortic state.

Gizzard adenocarcinoma in an aged Humboldt penguin (Spheniscus humboldti)

Spontaneous gizzard adenocarcinoma was found in a 15-year-old male Humboldt penguin (Spheniscus humboldti). The lesser curvature of the gizzard wall was extensively and markedly thickened with a hard white tumour mass. Histopathologically, the tumour in the gizzard consisted of two structures: small to large acini lined by cuboidal or flattened cells with poor stroma in the mucosa, and undifferentiated tumour cells arranged singly or in cords with acinar structures separated by dense fibrous tissue in the muscular layer. Small white metastatic tumours of the intestine and the pancreas had a similar histological appearance to that in the muscular layer of the gizzard. From the location of tumour in the gizzard and the stainability with combined alcian blue pH 2.5-periodic acid Schiff, it was considered that this tumour might originate from the lining cells of the tip of the gizzard mucosal folds.