FREQUENT DISRUPTION OF THE NF1 GENE BY A NOVEL MURINE AIDS VIRUS-RELATED PROVIRUS IN BXH-2 MURINE MYELOID LYMPHOMAS

Evi-2, a common site of viral integration in BXH-2 myeloid lymphomas, is located within a large intron of the Nfl tumor suppressor gene, Vir al integration at Evi-5 appears to induce disease by disrupting normal Nfl expression, During our attempts to characterize the nature of the proviruses located at Evi-2, we found that approximately half of the proviruses were defective nonecotropic proviruses (A. M. Buchberg, H. G. Bedigian, N. A. Jenkins, and N. G. Copeland, Mol. Cell, Biol, 10:46 58-4666, 1990). This was surprising, since most proviruses characteriz ed at other BXH-2 common integration sites are full-length ecotropic v iruses. In the studies described here, we found that this defective pr ovirus carries two large deletions, one in pol and one in env, and is structurally related to another murine retrovirus, the murine AIDS ret rovirus. By using oligonucleotide probes specific for this defective p rovirus, designated MRV, we showed that MRV-related proviruses are car ried as endogenous germ line proviruses in most inbred strains, In add ition, we identified the endogenous MRV provirus that gives rise to th e defective proviruses identified at Evi-2. We present a model that ac counts for the positive selection of MRV proviruses at Evi-2, which ma y allow selective identification of common viral integration sites har boring tumor suppressor genes.