AKV and AKR mink cell focus-forming virus-specific probes from the envelope and long terminal repeat (LTR) regions were prepared for study of the structure of recombinant proviruses in tumor tissues of AKR mice. The results showed that (i) all somatically acquired proviruses possessed, besides a recombinant gp7O gene, an altered U3 LTR; (ii) in a substantial portion of the somatically acquired AKR mink cell focusforming proviruses, the LTR comprised sequences derived from the same xenotropic-like provirus; (iii) this U3 LTR donating parental provirus (Xeno-dL) was present only once per genome equivalent in several mouse strains; (iv) in the strains containing the Xeno-dL provirus, the provirus was present in the same chromosomal site; (v) restriction analysis of the Xeno-dL revealed that the mink cell focus-forming gp7O sequences were derived from a parental provirus, different from Xeno-dL. Therefore, at least two nonecotropic parents participate in the generation of leukemogenic AKR mink cell focus-forming viruses: a xenotropic-like virus, Xeno-dL, donating U3 LTR sequences, and another xenotropic-like virus or viruses providing gp7O sequences.
Structures of somatically acquired murine leukemia virus (MuLV) genomes present in the DNA of a large panel of MuLV-induced C57BL and BALB/c B and non-T/non-B cell lymphomas were compared with those present in MuLV-induced T-cell lymphomas induced in the same low-"spontaneous"-lymphoma-incidence mice. Analyses were performed with probes specific for the gp70, p15E, and U3-long terminal repeat (LTR) regions of ecotropic AKV MuLV and a mink cell focus-forming virus (MCF)-LTR probe annealing with U3-LTR sequences of a unique endogenous xenotropic MuLV, which also hybridizes with U3-LTR sequences of a substantial portion of somatically acquired MCF genomes in spontaneous AKR thymomas. The DNAs of both T- and B-cell tumors induced by neonatal inoculation with the highly oncogenic C57BL-derived MCF 1233 virus predominantly contain integrated MCF proviruses. In contrast, the DNAs of more slowly developing B and non-T/non-B cell lymphomas induced by poorly oncogenic ecotropic or MCF C57BL MuLV isolates mostly contain somatically acquired ecotropic MuLV genomes. Approximately 50% of the spontaneous C57BL lymphoma DNAs contain somatically acquired MuLV genomes. None of the integrated MuLV proviruses annealed with the MCF-LTR probe, which indicates a clear difference in LTR structure with a substantial portion of the somatically acquired MuLV genomes present in the DNA of spontaneous AKR thymomas. This study stresses a dominant role of MuLV with ecotropic gp70 and LTR sequences in the development of slowly arising MuLV-induced B and non-T/non-B cell lymphomas.
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