Oncogene activation by retroviral DNA insertion has been implicated in a variety of neoplasms. The present application represents our continued effort to understand the molecular mechanisms involved in the induction of chicken B and T- lymphomas. In the past two years, we have focused on the characterization of a novel avian T-lymphoma identified by the CoPI. This lymphoma is induced by avian reticuloendotheliosis virus (REV) and resembles Marek's disease herpes virus (MDV) induced T-lymphoma. We have demonstrated that insertional activation of c-myc is involved in this disease, but the c-myc activation pattern differs from that found in B-lymphomas induced by the same virus. We have also characterized in detail the structure and expression of a provirus involved in c-myc activation in one B-lymphoma sample. Our studies, together with others, have revealed a number of interesting ways that retroviruses can modulate the LTR promoter activities and their interactions with host oncogenes. Understanding transcriptional modulation of viral LTR's and adjacent oncogenes are not only key to our understanding of the oncogene-activation process but also important in our appreciation of the complex eucaryotic transcriptional machinery. This represents a major focus of the present application. In addition, we wish to continue our investigation of the possible relationship between REV (retroviral) and MDV (herpes viral) induced T-lymphomas. In particular, we propose to further explore the structure and the significance of the REV LTR-related sequence we have recently identified in the pathogenic MDV genome. Finally, we propose to investigate the novel oncogene involved in rare B-lymphomas induced by avian retroviruses carrying endogenous LTR's.
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