ONCOGENIC DETERMINANTS OF THE EMERGING ALV-J RETROVIRUS

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DESCRIPTION: Avian leukemia virus-J (ALV-J) is a new non-acute transforming retrovirus that exhibits several biologically interesting features. First, ALV-J induces myeloid leukemias whereas most other ALV's induce primarily B cell lymphomas. Second, it has an envelope gene that specifies a novel subgroup (J). Third, different isolates of the virus show a high degree of genetic diversity in the env gene. Fourth, the ALV-J genome shows a complex relationship to previously described avian viruses and appears to have arisen by one or more recombination events between endogenous and exogenous viruses. Experiments in this proposal are designed to investigate several biological properties of ALV-J. Endogenous ALV-J env-related sequences have been identified that are not highly related to other viruses. Experiments are proposed (1) to determine whether evidence supports the hypothesis that these endogenous sequences contribute to the genetic diversity of infecting ALV-J virus and (2) to determine whether the presence and/or expression of the endogenous ALV-J env related sequences are associated with either an increased or decreased susceptibility to ALV-J induced malignancies. This suggestion is based on studies with murine, feline, and avian viruses that demonstrate that endogenous virus sequences can either limit or promote virus-induced disease by distinct and interesting mechanisms. Oncogenesis studies will also be conducted to investigate the unusual disease specificity of ALV-J. Two regions of ALV-J that are clearly distinct from other ALVs are the LTR and the env gene. Therefore, to determine whether either or both of these regions are important for induction of myeloid tumors by ALV-J, chimeric viruses will be generated between ALV-J and a traditional, B-lymphoma inducing strain of ALV that individually exchange the env and LTR regions and subsequently tested for oncogenicity in vivo. In addition, ALV-J induced tumors will be collected and the common integration site identified.