Moser T, Harbers K, Kratochwil K
Institute of Molecular Biology, Austrian Academy of Sciences, Salzburg, Austria.
Mol Cell Biol. 1996 Jan;16(1):384-9. doi: 10.1128/MCB.16.1.384.
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.
莫洛尼鼠白血病逆转录病毒（Mo-MuLV）的内源性前病毒在早期胚胎中被转录阻断，并且一般即使在组织对新整合拷贝的表达变得允许时仍保持沉默。最终，可能在极少数细胞中的激活引发快速的超级感染，导致病毒血症和白血病，但导致前病毒激活的过程尚不清楚。携带内源性Mo-MuLV的几种小鼠品系（Mov系）之间病毒血症的发生和发展差异归因于染色体位置效应，但任何品系的前病毒激活的细胞类型和阶段均未知。我们现在监测了Mov13品系中病毒转录本和颗粒的出现情况，该品系在具有明确转录活性的胶原基因（Col1a1）的第一个内含子中以反向方向携带Mo-MuLV前病毒。我们报告了成骨细胞和成牙本质细胞中存在必需的组织和阶段特异性病毒激活。这种激活模式的重要性体现在以下事实上：在表达野生型胶原基因的多种细胞中，只有这两种细胞类型也能转录包括其病毒插入片段的突变等位基因。我们提出，前病毒基因组的这种转录，尽管方向相反，会导致病毒启动子的激活。
