Leukemogenicity of Moloney murine leukemia viruses carrying polyoma enhancer sequences in the long terminal repeat is dependent on the nature of the inserted polyoma sequences.
The leukomogenicity of Moloney murine leukemia virus (M-MuLV) variants with chimeric long terminal repeats (LTRs) containing sequences from polyomavirus was studied. We previously showed that insertion of the B enhancer element from the PyF101 variant into the M-MuLV LTR between the M-MuLV enhancers and promoter abolished leukemogenicity. PyF101 differs from wild-type polyoma in that it can productively infect undifferentiated F9 embryonal carcinoma cells; this is due to alterations in the B enhancer element. Two additional chimeric M-MuLVs were generated that contained the B enhancers from wild-type polyoma and also from a second host range variant (PyF441), which differs from wild-type polyoma by only a single base change. In contrast to Mo+PyF101 M-MuLV, both Mo+Pywt and Mo+-PyF441 M-MuLV induced T-lymphoid leukemia in neonatal NIH Swiss mice with the same time course as wild-type M-MuLV. Thus the lack of leukemogenicity of Mo+PyF101 M-MuLV was related to the exact nature of the PyF101 B enhancers. While both Mo+Pywt and Mo+PyF441 M-MuLVs induced leukemia, they showed differences when the resulting tumors were examined. First, approximately one-third of the tumors induced by Mo+Pywt M-MuLV contained proviruses which lacked polyoma sequences, while all of the tumors induced by Mo+PyF441 M-MuLV contained proviruses with the chimeric LTR. Second, a majority of tumors induced by Mo+Pywt M-MuLV (and also wild-type, M-MuLV) showed proviral integrations near one or more of the cellular c-myc, pim-1, or pvt-1 loci. In contrast, tumors induced by Mo+PyF441 M-MuLV showed infrequent integrations at these loci.
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Department of Molecular Biology and Biochemistry, University of California, Irvine 92717.
Chute
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Chao
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Pattengale
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D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004274:DNA, Recombinant; D004279:DNA, Viral / Q000032:analysis; D004742:Enhancer Elements, Genetic; D007942:Leukemia, Experimental / Q000235:genetics* / Q000382:microbiology; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics* / Q000472:pathogenicity; D011120:Polyomavirus / Q000235:genetics*; D011519:Proto-Oncogenes; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D013045:Species Specificity
D004273:DNA, Neoplasm; D004274:DNA, Recombinant; D004279:DNA, Viral