Tissue- and stage-specific activation of an endogenous provirus after transcription through its integration site in the opposite orientation.

AUTOR(ES)

Moser, T

RESUMO

Endogenous proviruses of the Moloney murine leukemia retrovirus (Mo-MuLV) are transcriptionally blocked in early embryos and in general remain silent even when the tissues have become permissive to the expression of newly integrated copies. Eventually, activation in presumably very few cells initiates rapid superinfection leading to viremia and leukemia, but the processes leading to provirus activation are unknown. Differences in the onset and development of viremia between several mouse strains carrying an endogenous Mo-MuLV (Mov lines) are attributed to a chromosomal position effect, but neither cell type nor stage of provirus activation is known for any strain. We have now monitored the appearance of viral transcripts and particles in the Mov13 strain, which carries the Mo-MuLV provirus in inverted orientation in the first intron of a collagen gene (Col1a1) with well-characterized transcriptional activity. We report obligatory tissue- and stage-specific virus activation in osteoblasts and odontoblasts. The significance of this activation pattern is indicated by the fact that of the great variety of cells 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.

Documentos Relacionados

• Tissue- and stage-specific modulation of Wingless signaling by the segment polarity gene lines
• Ovule development: identification of stage-specific and tissue-specific cDNAs.
• Tissue- and developmental stage-specific forms of a neural cell surface antigen linked to differences in glycosylation of a common polypeptide.
• Developmental regulation of the human embryonic beta-like globin gene is mediated by synergistic interactions among multiple tissue- and stage-specific elements.
• Highly conserved proximal promoter element harbouring paired Sox9-binding sites contributes to the tissue- and developmental stage-specific activity of the matrilin-1 gene