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

Although the murine retrovirus SL3-3 is highly leukaemogenic, in both the structure of its genome and in its properties of replication in tissue culture it closely resembles the nonleukaemogenic 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). 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 lies 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.