Retrovirus activation in embryonal carcinoma cells by cellular promoters

Retrovirus expression in embryonal carcinoma (EC) cells is blocked at a postintegration stage of the viral life cycle, because of the inadequate function of the viral long terminal repeat (LTR) promoter in this cell type. However, rare sites in the EC cell genome permit provirus expression by undefined mechanisms. Our analysis of three expressed proviruses indicates that they have inserted into actively transcribed regions. Two of the three, examined in detail, integrated into the first introns of cellular transcription units in close proximity to active cellular promoters. One of these cellular genes is the probable murine homolog of the yeast ribosomal protein L3, responsible for trichodermin resistance. In all cases, virus activation appears to involve production of viral transcripts that are initiated in the 5'-flanking region, transcribed through the viral LTR, and subsequently spliced from a cellular donor to a viral acceptor. Our results suggest a general procedure for the isolation of active genes and promoters in different tissues.