Sørensen Karina Dalsgaard, Sørensen Annette Balle, Quintanilla-Martinez Leticia, Kunder Sandra, Schmidt Jörg, Pedersen Finn Skou
Department of Molecular Biology, University of Aarhus, C.F. Møllers Allé, Building 130, DK-8000 Aarhus C, Denmark.
Virology. 2005 Apr 10;334(2):234-44. doi: 10.1016/j.virol.2005.01.039.
Murine leukemia viruses (MLVs) can be lymphomagenic and bone pathogenic. In this work, the possible roles of two distinct proviral enhancer nuclear factor 1 (NF1) binding sites in osteopetrosis and tumor induction by B-lymphomagenic Akv1-99 MLV were investigated. Akv1-99 and mutants either with NF1 site 1, NF1 site 2 or both sites disrupted induced tumors (plasma cell proliferations by histopathology) with remarkably similar incidence and mean latency in inbred NMRI mice. Clonal immunoglobulin gene rearrangement detection, by Southern analysis, confirmed approximately half of the tumors induced by each virus to be plasmacytomas while the remaining lacked detectable clonally rearranged Ig genes and were considered polyclonal; a demonstration that enhancer NF1 sites are dispensable for plasmacytoma induction by Akv1-99. In contrast, X-ray analysis revealed significant differences in osteopetrosis induction by the four viruses strongly indicating that NF1 site 2 is critical for viral bone pathogenicity, whereas NF1 site 1 is neutral or moderately inhibitory. In conclusion, enhancer NF1 sites are major determinants of osteopetrosis induction by Akv1-99 without significant influence on viral oncogenicity.
鼠白血病病毒（MLVs）可致淋巴瘤和骨骼病变。在本研究中，我们探究了两个不同的前病毒增强子核因子1（NF1）结合位点在B淋巴细胞致瘤性Akv1 - 99 MLV诱导骨硬化和肿瘤形成过程中的可能作用。Akv1 - 99及其NF1位点1、NF1位点2或两个位点均被破坏的突变体在近交系NMRI小鼠中诱导肿瘤（通过组织病理学检测为浆细胞增殖），其发生率和平均潜伏期非常相似。通过Southern分析进行的克隆免疫球蛋白基因重排检测证实，每种病毒诱导的肿瘤中约一半为浆细胞瘤，而其余肿瘤缺乏可检测到的克隆性重排Ig基因，被认为是多克隆的；这表明增强子NF1位点对于Akv1 - 99诱导浆细胞瘤并非必需。相比之下，X射线分析显示这四种病毒在诱导骨硬化方面存在显著差异，强烈表明NF1位点2对病毒的骨骼致病性至关重要，而NF1位点1则是中性或具有中等抑制作用。总之，增强子NF1位点是Akv1 - 99诱导骨硬化的主要决定因素，对病毒致癌性无显著影响。
