Yuen P H, Szurek P F
Science Park-Research Division, M. D. Anderson Cancer Center, University of Texas, Smithville 78957.
J Virol. 1989 Feb;63(2):471-80. doi: 10.1128/JVI.63.2.471-480.1989.
Chimeric constructs were generated by exchanging genomic fragments between the potent T-cell lymphoma inducer Moloney murine leukemia virus (MoMuLV) and its derivative MoMuLV-TB, which induces T-cell lymphoma after a relatively longer latent period. Analysis of the T-cell lymphoma-inducing potential of the hybrid viruses that were obtained localized the primary determinant critical to efficient T-cell lymphoma induction to the MoMuLV ClaI-XbaI fragment which comprises 48 nucleotides (nt) of p15E, p2E, the 3'-noncoding sequence, and 298 nt of U3. The 438-base-pair ClaI-XbaI fragments of MoMuLV and MoMuLV-TB differed in only 11 nt. Nine mutations were found within the enhancer. These mutations occurred within the two CORE, the two GRE-LVa, and two of the four NF1 nuclear factor-binding motifs. MoMuLV-TB replicated better than MoMuLV in thymus-bone marrow (TB) cells, a cultured cell line of lymphoid origin. In addition, MoMuLV-TB and NwtTB-2, a recombinant virus with the ClaI-SmaI fragment of MoMuLV-TB in a MoMuLV background, replicated in thymocytes as efficiently as did MoMuLV or TBNwt-2, the reciprocal recombinant virus, with the ClaI-SmaI fragment of MoMuLV in a MoMuLV-TB background. Like NwtTB-4, a recombinant virus with the ClaI-XbaI fragment of MoMuLV-TB in a MoMuLV background, NwtTB-2 induced lymphoma after a long latent period. The finding given above suggests that thymotropism is not the only factor that determines the T-cell lymphoma-inducing potential of MoMuLV. It appears likely that mutations in one or more of the MoMuLV-TB nuclear factor-binding motifs may have altered the interaction of the enhancer with specific nuclear factors; this, in turn, may affect the T-cell lymphoma-inducing potential of MoMuLV-TB.
通过在强效T细胞淋巴瘤诱导剂莫洛尼鼠白血病病毒（MoMuLV）及其衍生物MoMuLV-TB之间交换基因组片段，构建了嵌合基因。MoMuLV-TB在相对较长的潜伏期后可诱导T细胞淋巴瘤。对所获得的杂交病毒诱导T细胞淋巴瘤的潜力进行分析，将高效诱导T细胞淋巴瘤的主要决定因素定位到MoMuLV ClaI-XbaI片段，该片段包含p15E的48个核苷酸（nt）、p2E、3'-非编码序列以及U3的298个nt。MoMuLV和MoMuLV-TB的438个碱基对的ClaI-XbaI片段仅在11个nt上存在差异。在增强子内发现了9个突变。这些突变发生在两个CORE、两个GRE-LVa以及四个NF1核因子结合基序中的两个基序内。MoMuLV-TB在胸腺-骨髓（TB）细胞（一种淋巴源性培养细胞系）中的复制能力比MoMuLV更强。此外，MoMuLV-TB和NwtTB-2（一种在MoMuLV背景下含有MoMuLV-TB的ClaI-SmaI片段的重组病毒）在胸腺细胞中的复制效率与MoMuLV或TBNwt-2（在MoMuLV-TB背景下含有MoMuLV的ClaI-SmaI片段的反向重组病毒）一样高。与NwtTB-4（一种在MoMuLV背景下含有MoMuLV-TB的ClaI-XbaI片段的重组病毒）一样，NwtTB-2在长时间潜伏期后诱导淋巴瘤。上述发现表明，嗜胸腺性并非决定MoMuLV诱导T细胞淋巴瘤潜力的唯一因素。MoMuLV-TB的一个或多个核因子结合基序中的突变可能改变了增强子与特定核因子的相互作用；反过来，这可能会影响MoMuLV-TB诱导T细胞淋巴瘤的潜力。
