This long-standing project studies virus factors that influence the induction of neoplastic and non-neoplastic diseases by murine leukemia viruses (MuLVs). MuLVs studied have included the Moloney and Friend ecotropic (mouse cell-tropic) isolates, mink cell focus-inducing (MCF) viruses from AKR mice and other sources, ecotropic and amphotropic viruses isolated from wild mice and the defective BM5 immunodeficiency MuLV. Most recently we have studied the mouse strains CFW (commonly selected for carcinogenesis studies as a low lymphoma incidence mouse) and the several lines of NFS.Akv and NFS.C58v (NFS.V+ strains) that express high levels of ecotropic and often MCF classes of MuLV and develop spontaneous lymphoma of relatively long latency. Of particular interest is the high frequency of B cell lymphomas of a broad morphological spectrum, 90% of which carry new integrations of ecotropic MuLV. Viruses isolated in tissue culture from both CFW and NFS.V+ mice have been found to induce lymphoma in mice of a very low incidence, virus negative strain, these lymphomas occurring in much the same variety as seen in the donor strains. Both ecotropic and MCF viruses seem to have pathogenic activity.Inoculation of mice with the Moloney isolate of MuLV causes thymic lymphoma and a specific region of the viral genome (called the enhancer core) has been shown to be critical for induction of this type of disease. A cellular protein (CBF) that is highly expressed in thymus binds to this region. Using viruses mutated in these core sequences and having different binding affinities, it was found that CBF does play a role in disease induction. Viruses with high affinity binding induced disease with a shorter latent period than those with lower affinity and the disease was more likely to be lymphoma of the T-cell, thymic type. This study was performed in collaboration with investigators at Dartmouth Medical School. - Mice, B-cell lymphoma, murine leukemia viruses, core binding factor (CBF)
