TISSUE-SPECIFIC AND STAGE-SPECIFIC ACTIVATION OF AN ENDOGENOUS PROVIRUS AFTER TRANSCRIPTION THROUGH ITS INTEGRATION SITE IN THE OPPOSITE ORIENTATION

Endogenous proviruses of the Moloney murine leukemia retrovirus (Mo-Mu LV) are transcriptionally blocked in early embryos and in general rema in silent even when the tissues have become permissive to the expressi on of newly integrated copies. Eventually, activation in presumably ve ry few cells initiates rapid superinfection leading to viremia and leu kemia, but the processes leading to provirus activation are unknown. D ifferences in the onset and development of viremia between several mou se strains carrying an endogenous Mo-MuLV (Mov lines) are attributed t o a chromosomal position effect, but neither cell type nor stage of pr ovirus activation is known for any strain. We have now monitored the a ppearance of viral transcripts and particles in the Mov13 strain, whic h carries the Mo-MuLV provirus in inverted orientation in the first in tron of a collagen gene (Col1a1) with well-characterized transcription al activity. We report obligatory tissue- and stage-specific virus act ivation in osteoblasts and odontoblasts. The significance of this acti vation pattern is indicated by the fact that of the great variety of c ells expressing the wild-type collagen gene, only these two cell types can also transcribe the mutant allele including its viral insert. We propose that this transcription of the proviral genome, albeit in the opposite direction, leads to the activation of the viral promoter.