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

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.