GENETIC STRUCTURE OF MURINE RETROVIRUSES

本项目目前的目标是识别和描述

The current objectives of this project are to identify and characterize the types of recombinants generated between ecotropic murine leukemia virus (MuLVs) and endogenous retroviral gene sequences. Analyses of recombinant polytropic viruses generated after inoculation of mice with different ecotropic MuLVs demonstrated that different MuLVs specifically recombine with particular endogenous retroviral sequences to generate recombinants. Polytropic viruses derived from different endogenous sequences exhibited different biological properties, including their oncogenicity and their in vitro host ranges. Analyses of polytropic viruses generated after inoculation of in vitro-constructed recombinants between ecotropic MuLVs which differ in their specificity of recombination have identified the 3' LTR of the viral genome as a region which influences the specificity. AKR/J mice harbor endogenous ecotropic viruses and exhibit a high incidence of spontaneous lymphomas. Utilizing an immunofluorescence assay with monoclonal antibodies, two novel types of recombinant viruses have been identified in preleukemic ADR/J mice. Recombinant viruses were isolated from the spleens of mice as young as 1 month of age. These isolates possess antigens characteristic of polytropic viruses but exhibit a more limited in vitro host range. In contrast to polytropic viruses, they do not infect SC-1 (mouse) or mink lung fibroblasts, but are highly infectious for a Mus dunni cell line. At about 4 months of age, a second type of recombinant virus was identified in the thymuses. SC-1, mink and Mus dunni cells could only be infected with these recombinants by co-cultivation with thymocytes. These two types of recombinant MuLVs are the earliest and the most prevalent recombinants found in preleukemic mice and their role in leukemogenesis is under investigation.