Oncogenicity and U3 region sequences of class II recombinant MuLVs of CWD mice

The pathogenic potential of Class II env recombinant murine leukemia viruses (MuLV) found in the high leukemia strain CWD has not been defined. We found that neonatal CWD mice that were injected with the phenotypic mixture of the spontaneous CWD class II env recombinant, CWM-T-15, and the AKR endogenous ecotropic virus, Akv 623, developed non-T-cell lymphomas more rapidly than controls inoculated with either virus alone or with a CWD ecotropic virus. In contrast, CWN-T-25, a class II env MuLV that was recovered from a CWD mouse injected with the AKR ecotropic virus SL3-3, dramatically accelerated the onset of T-cell lymphomas in the same assay. Southern blots of the tumor DNAs from each set of animals revealed the integration of recombinant and ecotropic proviruses. We also found that there were differences in the nucleotide sequences of the viral enhancer elements of the CWD viruses. The results indicate that (1) the two CWD class II env recombinants that were tested contained oncogenic determinants; (2) phenotypic mixing with ecotropic viruses was required for the full expression of the pathogenic potential of the CWM-T-15 recombinant; and (3) the distinct phenotypes of the CWD viruses likely reflected the differences in the origin of the viral enhancer element.