Determination of the leukaemogenicity of a murine retrovirus by sequences within the long terminal repeat

Jack Lenz, Daniel Celander, Robert L. Crowther, Roberto Patarca, Dennis W. Perkins, William A. Haseltine

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Abstract

Although the murine retrovirus SL3-3 is highly leukaemo-genic 1,2, in both the structure of its genome and in its properties of replication in tissue culture it closely resembles the non-leukaemogenic retrovirus Akv (refs 3, 4). An.earlier investigation of the properties of recombinant SL3-3-Akv viruses localized the major determinant of leukaemogenicity outside the env gene, in a region of the viral genome that includes the gag gene and the noncoding long terminal repeat (LTR)4. To localize the determinant of SL3-3's leukaemogenicity more precisely we have now construced a recombinant provirus containing the LTR of SL3-3 and the coding region of Akv. The leukaemogenicity of these recombinants demonstrates that the determinant of leukaemogenicity ties within the SL3-3 LTR. Nucleotide sequencing of the LTRs of SL3-3 and Akv shows that they differ by a set of changes in the region thought to contain a transcriptional enhancer element. We suggest that enhancer region sequences are the major determinants of leukaemogenicity in these viruses.

Original languageEnglish (US)
Pages (from-to)467-470
Number of pages4
JournalNature
Volume308
Issue number5958
DOIs
StatePublished - Dec 1 1984
Externally publishedYes

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    Lenz, J., Celander, D., Crowther, R. L., Patarca, R., Perkins, D. W., & Haseltine, W. A. (1984). Determination of the leukaemogenicity of a murine retrovirus by sequences within the long terminal repeat. Nature, 308(5958), 467-470. https://doi.org/10.1038/308467a0