The oncologist's debt to the chicken

Weiss, Robin A.

doi:10.1080/03079459808419287

Cited by 6 publications

(4 citation statements)

References 56 publications

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“…In contrast, Marek's Disease Virus (MDV) is a widespread, oncogenic α-herpesvirus infection of chickens which readily causes lymphoid tumors and has immense impact on the poultry industry [4] . The oncogenicity of MDV, combined with the ability to vaccinate against tumor formation make the MDV-chicken system an excellent natural infection model for understanding the biology and treatment of viral induced lymphomas [1] , [5] – [7] .…”

Section: Introductionmentioning

confidence: 99%

Clonal Structure of Rapid-Onset MDV-Driven CD4+ Lymphomas and Responding CD8+ T Cells

et al. 2011

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Lymphoid oncogenesis is a life threatening complication associated with a number of persistent viral infections (e.g. EBV and HTLV-1 in humans). With many of these infections it is difficult to study their natural history and the dynamics of tumor formation. Marek's Disease Virus (MDV) is a prevalent α-herpesvirus of poultry, inducing CD4+ TCRαβ+ T cell tumors in susceptible hosts. The high penetrance and temporal predictability of tumor induction raises issues related to the clonal structure of these lymphomas. Similarly, the clonality of responding CD8 T cells that infiltrate the tumor sites is unknown. Using TCRβ repertoire analysis tools, we demonstrated that MDV driven CD4+ T cell tumors were dominated by one to three large clones within an oligoclonal framework of smaller clones of CD4+ T cells. Individual birds had multiple tumor sites, some the result of metastasis (i.e. shared dominant clones) and others derived from distinct clones of transformed cells. The smaller oligoclonal CD4+ cells may represent an anti-tumor response, although on one occasion a low frequency clone was transformed and expanded after culture. Metastatic tumor clones were detected in the blood early during infection and dominated the circulating T cell repertoire, leading to MDV associated immune suppression. We also demonstrated that the tumor-infiltrating CD8+ T cell response was dominated by large oligoclonal expansions containing both “public” and “private” CDR3 sequences. The frequency of CD8+ T cell CDR3 sequences suggests initial stimulation during the early phases of infection. Collectively, our results indicate that MDV driven tumors are dominated by a highly restricted number of CD4+ clones. Moreover, the responding CD8+ T cell infiltrate is oligoclonal indicating recognition of a limited number of MDV antigens. These studies improve our understanding of the biology of MDV, an important poultry pathogen and a natural infection model of virus-induced tumor formation.

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Section: Introductionmentioning

confidence: 99%

Clonal Structure of Rapid-Onset MDV-Driven CD4+ Lymphomas and Responding CD8+ T Cells

et al. 2011

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“…After infection with any given MDV strain, gross T-cell-predominant lymphomas form only in individual chickens that have susceptible genotypes (18). MDV is an accepted and naturally occurring in vivo animal model of herpesvirus oncology (18,30,105), but in common with other animal models, a major impediment to its utility is that the neoplastically transformed cells in MD lymphoma have not been identified. Previous work has suggested that a monoclonal antibody (MAb), AV37, recognizing a novel surface antigen expressed by MDV-transformed cell lines (MDCC) in vitro, identifies the neoplastically transformed cells in MD lymphomas (14,15,85).…”

mentioning

confidence: 99%

Identification of the Neoplastically Transformed Cells in Marek's Disease Herpesvirus-Induced Lymphomas: Recognition by the Monoclonal Antibody AV37

Burgess¹,

Davison²

2002

J Virol

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Understanding the interactions between herpesviruses and their host cells and also the interactions between neoplastically transformed cells and the host immune system is fundamental to understanding the mechanisms of herpesvirus oncology. However, this has been difficult as no animal models of herpesvirus-induced oncogenesis in the natural host exist in which neoplastically transformed cells are also definitively identified and may be studied in vivo.

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“…20,21,51 Herpesviruses have been associated with neoplasia in general, and lymphomas in particular, in humans and other species. Marek's disease (MD), an established model of herpesvirus-induced lymphoma, 9,60 is caused by an oncogenic ␣-herpesvirus (Marek's disease virus [MDV]) of chickens. We have studied this complex disease 9,46 in order to determine whether genotype-dependent tumor regression or progression occurs.…”

mentioning

confidence: 99%

Resistance to Marek's Disease Herpesvirus-induced Lymphoma is Multiphasic and Dependent on Host Genotype

Burgess¹,

Başaran

Davison³

2001

Vet Pathol

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Abstract. Genotype-dependent differences in Marek's disease (MD) susceptibility were identified using 14-day-old line N and 6 1 (resistant) and 15I and 7 2 (susceptible) inbred chickens infected with HPRS-16 MD virus (MDV). All line 7 2 chickens developed progressive MD. Line 15I had fluctuating MD-specific clinical signs and individuals recovered. A novel histologic scoring system enabled indices to be calculated for lymphocyte infiltration into nonlymphoid organs. All genotypes had increased mean lesion scores (MLSs) and mean total lesion scores after MDV infection. These differed quantitatively and qualitatively between the genotypes. Lines 6 1 and 7 2 had a similar MLS distribution in the cytolytic phase, although scores were greater in line 7 2 . At the time lymphomas were visible in line 7 2 , histologic lesions in line 6 1 were regressing. AV37 ϩ cells were present in similar numbers in all genotypes in the cytolytic phase, suggesting that neoplastically transformed cells were present in all genotypes regardless of MD susceptibility. After the cytolytic phase, AV37ϩ cell numbers increased in lines 7 2 and 15I but decreased in lines 6 1 and N. In the cytolytic and latent phases, in all genotypes, most infiltrating cells were CD4 ϩ . After this time, line 7 2 and 15I lesions increased in size and most cells were CD4 ϩ ; line 6 1 and N lesions decreased in size and most cells were CD8ϩ . In all genotypes, AV37 immunostaining was weak in lesions with many CD8 ϩ cells, suggesting that AV37 antigen expression or AV37 ϩ cells were controlled by CD8 ϩ cells. The rank order, determined by clinical signs and pathology, for MD susceptibility (highest to lowest) was 7 2 Ͼ 15I Ͼ 6 1 Ͼ N.

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The oncologist's debt to the chicken

Cited by 6 publications

References 56 publications

Clonal Structure of Rapid-Onset MDV-Driven CD4+ Lymphomas and Responding CD8+ T Cells

Clonal Structure of Rapid-Onset MDV-Driven CD4+ Lymphomas and Responding CD8+ T Cells

Identification of the Neoplastically Transformed Cells in Marek's Disease Herpesvirus-Induced Lymphomas: Recognition by the Monoclonal Antibody AV37

Resistance to Marek's Disease Herpesvirus-induced Lymphoma is Multiphasic and Dependent on Host Genotype

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