We previously described an enhancer variant of Moloney murine leukaemia virus (M-MuLV), ΔMo + SV M-MuLV, in which the enhancers of MuLV have been deleted and replaced with the enhancers of the simian virus 40 (SV40). When this virus is injected into neonatal NIH Swiss mice, pre-B and B-lymphoblastic lymphomas develop with a latency of 17 months. Van Lohuizen (1989) described a line of transgenic mice that carry an activated -1 proto-oncogene transgene (Eµ -1). They also reported that Eµ -1 transgenic mice show greatly accelerated lymphoma development when infected with wild-type M-MuLV at birth. In these experiments, neonatal Eµ -1 transgenic mice were infected intraperitoneally with ΔMo + SV M-MuLV. Marked acceleration of T-lymphoid leukaemia was seen. However, 10 of the 11 tumours analysed were found to be negative for the SV40 enhancers, but they still contained M-MuLV DNA as measured by Southern blot analysis. The LTRs on viruses cloned from two such tumours (as well as on virus recovered by infection onto NIH 3T3 cells) were characterized by PCR amplification, molecular cloning and sequence analysis. The LTR's from the two tumours were identical to each other and were distinct from both the ΔMo + SV M-MuLV and wild-type M-MuLV LTRs. However, they were identical to a rearranged solo M-MuLV LTR present in the Eµ -1 transgene. These results indicate that the recombination between ΔMo + SV M-MuLV and the Eµ -1 transgene yielded a replication-competent and pathogenic virus at high efficiency. This is the first report of recombination between an exogenous MuLV and a solo endogenous LTR.


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