Origins of enhancer sequences of recombinant murine leukemia viruses from spontaneous B- and T-cell lymphomas of CWD mice.

Recombinant murine leukemia viruses from the highly leukemic mouse strains AKR, HRS, and C58 usually acquire pathogenic U3 region sequences fro the endogenous xenotropic virus, Bxv-1. However, the majority of tumors from another highly leukemic strain, CWD, contained recombinant viruses that lacked Bxv-1-specific sequences. The nucleotide sequence of the U3 regions of two such CWD recombinants was nearly identical to that of the endogenous ecotropic virus parent Emv-1, but they shared three nucleotide substitutions immediately 3' of the enhancer core. These substitutions were found in recombinant proviruses from about one-third of spontaneous CWD lymphomas as determined by an oligonucleotide hybridization assay of proviral fragments that had been nucleotide substitutions in the CWD viruses were inherited from an endogenous polytropic provirus that is absent in the other highly leukemic strains. On the basis of the results of these and previous studies, we propose that CWD recombinants acquire pathogenic U3 region sequences through recombination with an endogenous polytropic virus or Bxv-1 and that the pathogenicity of these sequences may be related to a sequence motif that is known to bind members of the basic helix-loop-helix class of transcription factors.