Rohn J L, Lauring A S, Linenberger M L, Overbaugh J
Department of Microbiology, University of Washington, Seattle 98195, USA.
J Virol. 1996 Nov;70(11):8071-80. doi: 10.1128/JVI.70.11.8071-8080.1996.
Feline leukemia virus (FeLV) is thought to induce neoplastic diseases in infected cats by a variety of mechanisms, including the transduction of host proto-oncogenes. While FeLV recombinants that encode cellular sequences have been isolated from tumors of naturally infected animals, the acquisition of an unrelated host gene has never been documented in an experimental FeLV infection. We isolated recombinant FeLV proviruses encoding feline Notch2 sequences from thymic lymphoma DNA of two cats inoculated with the molecularly cloned virus FeLV-61E. Four recombinant genomes were identified, three in one cat and one in the other. Each had similar but distinct transduction junctions, and in all cases, the insertions replaced most of the envelope gene with a region of Notch2 that included the intracellular ankyrin repeat functional domain. The product of the FeLV/Notch2 recombinant provirus was a novel, truncated 65- to 70-kD Notch2 protein that was targeted to the cell nucleus. This virally encoded Notch2 protein, which resembles previously constructed, constitutively activated forms of Notch, was apparently expressed from a subgenomic transcript spliced at the normal envelope donor and acceptor sequences. The data reported here implicate a nuclear, activated Notch2 protein in FeLV-induced leukemogenesis.
猫白血病病毒（FeLV）被认为通过多种机制在受感染的猫中诱发肿瘤性疾病，包括转导宿主原癌基因。虽然已从自然感染动物的肿瘤中分离出编码细胞序列的FeLV重组体，但在实验性FeLV感染中从未记录到获得无关宿主基因的情况。我们从两只接种了分子克隆病毒FeLV-61E的猫的胸腺淋巴瘤DNA中分离出编码猫Notch2序列的重组FeLV前病毒。鉴定出四个重组基因组，其中三只在一只猫中，一只在另一只猫中。每个重组基因组都有相似但不同的转导连接点，在所有情况下，插入片段都用包含细胞内锚蛋白重复功能域的Notch2区域取代了大部分包膜基因。FeLV/Notch2重组前病毒的产物是一种新型的、截短的65至70kD的Notch2蛋白，该蛋白定位于细胞核。这种病毒编码的Notch2蛋白类似于先前构建的、组成性激活的Notch形式，显然是从在正常包膜供体和受体序列处剪接的亚基因组转录本中表达的。此处报道的数据表明核内活化的Notch2蛋白与FeLV诱导的白血病发生有关。
