title: 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.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine 92717.
authors.forename: H
authors.initials: H
authors.lastname: Fan
authors.forename: H
authors.initials: H
authors.lastname: Chute
authors.forename: E
authors.initials: E
authors.lastname: Chao
authors.forename: P K
authors.initials: PK
authors.lastname: Pattengale
mesh_terms: 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
chemical_list: D004273:DNA, Neoplasm; D004274:DNA, Recombinant; D004279:DNA, Viral