The Moloney murine leukemia virus enhancer and its flanking sequences collaborate to determine virulence in T-cell lymphomagenesis

A panel of recombinant virus genomes was constructed by exchanging homologous genome fragments between the potent T-cell lymphoma inducer Moloney murine leukemia virus (MoMuLV) and its closely related but significantly less virulent relative MoMuLV-TB. Testing of these recombinant viruses in BALB/c mice established that only nucleotide changes within the Clal(-590)-Kpnl(36) fragment altered virulence. Fine analysis of this fragment showed that while mutations within the enhancer of MoMuLV-TB attenuated the latency period most, mutations within the MoMuLV-TB fragments flanking the enhancer also helped reduce the virulence of MoMuLV. The present study also suggests that the small difference in the relative number of lymphomas that developed primarily in the spleens of MoMuLV- or MoMuLV-TB-infected mice may correlate with nucleotide differences between the Clal-Kpnl fragments of the two viruses. However, the significantly greater proportion of premature death observed in MoMuLV-TB-relative to MoMuLV-infected mice could not be correlated with nucleotide differences in a specific genome fragment.