Tissue specific transcription from murine leukemia retroviruses

Abstract

Recombination studies have established that retroviral long terminal repeats (LTRs) are important genetic determinants of the viral capacity to induce hematopoietic tumors and to specify the type of cell comprising the tumor. Plasmids containing LTRs of several murine leukemia viruses (MuLV) linked to the chloramphenicol acetyltransferase (CAT) gene were tested in transient assays to measure relative levels of transcriptional activity in different types of hematopoietic cells. The relative level of LTR-driven expression in various types of cells corresponded to the type of tumor caused by the intact virus in vivo. Expression was not an all or none effect. Each LTR functioned in any cell type into which it was introduced. However, a particular LTR worked 4-to-20 fold better in the target cell for leukemogenesis. These results provided direct evidence that the transcriptional activity of LTRs plays a critical role in determining the target cell for retroviral oncogenesis.;LTR expression within the T lymphocyte lineage was used to investigate the mechanisms underlying cell-type specificity. Several cell lines with the properties of prothymocytes were tested and found to exhibit the same relative levels of LTR-Cat expression as was seen in T-lymphoma lines. However, a single cytotoxic T-cell line was tested and found to present a quite distinct profile of relative LTR-Cat expression. These data are consistent with the possibility that cells at earlier stages of differentiation may be the targets for viral lymphomagenesis.