Tissue-specific transcription preference as a determinant of cell tropism and leukaemogenic potential of murine retroviruses

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Abstract
Inoculation of susceptible strains of mice with the SL3-3 strain of murine leukaemia viruses induces T-cell lymphomas, whereas injection of the Akv strain does not1–3. Recombinant viruses that contain the long terminal repeat (LTR) of the SL3-3 virus and the gag, pol and env genes of the Akv virus are also leukaemogenic4. The cell-type specificity of leukaemias induced by viruses containing different LTR sequences is due in part to the ability of the virus to replicate in the appropriate cellular environment5–7. One explanation of the role of the LTR in determination of both cell tropism and leukaemogenic potential is that the LTR encodes tissue-permissive transcriptional elements. We report here that there are differences in the transcriptional activity of the SL3-3 and Akv LTR sequences in different murine cell types, and that the sequences present in the LTR of SL3-3 exhibit significantly enhanced transcriptional activity in T cells compared with the corresponding region of the Akv LTR. The results suggest that transcriptional elements are primary determinants of cell tropism and of leukaemogenicity of these viruses.