ORIGINS OF ENHANCER SEQUENCES OF RECOMBINANT MURINE LEUKEMIA VIRUSES FROM SPONTANEOUS B-CELL AND T-CELL LYMPHOMAS OF CWD MICE

Recombinant murine leukemia viruses from the highly leukemic mouse str ains AKR, HRS, and C58 usually acquire pathogenic U3 region sequences from 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 t o that of the endogenous ecotropic virus parent Emv-1, but they shared three nucleotide substitutions immediately 3' of the enhancer core. T hese substitutions were found in recombinant proviruses from about one -third of spontaneous CWD lymphomas as determined by an oligonucleotid e hybridization assay of proviral fragments that had been amplified by PCR. Analysis of amplified endogenous murine leukemia virus sequences suggested that the three nucleotide substitutions in the CWD viruses were inherited from an endogenous polytropic provirus that is absent i n the other highly leukemic strains. On the basis of the results of th ese and previous studies, we propose that CWD recombinants acquire pat hogenic U3 region sequences through recombination with an endogenous p olytropic 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 t he basic helix-loop-helix class of transcription factors.