The piscine retroviruses and their associate neoplasias are new models of oncogenesis. Walleye dermal sarcomas are associated with the presence of a complex retrovirus, walleye dermal sarcoma virus (WDSV). These sarcomas naturally develop and regress making them unique in the study of tumor biology. Walleye dermal sarcoma is transmissible to walleye fingerlings. This transmission is efficient, and disease induction is rapid. Only cell-free homogenates from regressing tumors, not from developing tumors, can transmit disease. Viral-gene expression and proviral burden are also significantly different in developing vs. regressing tumors: Only low levels of spliced accessory gene transcripts are present during tumor development, whereas high levels of all viral transcripts and virus are found in regressing tumors. The accessory genes, named as open reading frames, a, b, and c, presumably function in WDSV biology. The product of orf a is a cyclin homologue or """"""""retroviral cyclin?T. The products of orf b and orf c have no clear homologies. We hypothesize that the accessory proteins are oncogenic, control changes in virus expression, and induce tumor regression. Significant progress has been made in the characterization of both novel and precedented mechanisms involved in these processes. The goals of this proposal are to further characterize the functions of the WDSV accessory proteins in the control of general transcription factors, cell proliferation, and apoptosis. Work will proceed with full characterization of interacting cellular proteins and functional assays of transcription, signal transduction, and mitochondrial targeting. These studies will support the long-term objective of delineating general mechanisms of tumor induction and regression.
