The reduced virulence of the thymotropic Moloney murine leukemia virus derivative MoMuLV-TB is mapped to 11 mutations within the U3 region of the long terminal repeat
The reduced virulence of the thymotropic Moloney murine leukemia virus derivative MoMuLV-TB is mapped to 11 mutations within the U3 region of the long terminal repeat
复制标题
亲胸腺莫洛尼鼠白血病病毒衍生物 MoMuLV-TB 的毒力降低归因于长末端重复 U3 区域内的 11 个突变
作者：
P. H. Yuen;P. Szurek
通过在有效的 T 细胞淋巴瘤诱导剂莫洛尼鼠白血病病毒 (MoMuLV) 与其衍生物 MoMuLV-TB 之间交换基因组片段，生成嵌合构建体，MoMuLV-TB 在相对较长的潜伏期后诱导 T 细胞淋巴瘤。对所获得的杂交病毒诱导 T 细胞淋巴瘤的潜力的分析将有效诱导 T 细胞淋巴瘤的主要决定因素定位于 MoMuLV ClaI-XbaI 片段，该片段包含 p15E、p2E、3'-非编码序列的 48 个核苷酸 (nt) 和 U3 的 298 个核苷酸。 MoMuLV 和 MoMuLV-TB 的 438 个碱基对的 ClaI-XbaI 片段仅存在 11 nt 差异。在增强子内发现了九个突变。这些突变发生在两个 CORE、两个 GRE-LVa 和四个 NF1 核因子结合基序中的两个内。 MoMuLV-TB 在胸腺骨髓 (TB) 细胞（一种淋巴来源的培养细胞系）中复制得比 MoMuLV 更好。此外，MoMuLV-TB和NwtTB-2（一种在MoMuLV背景下具有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背景下具有MoMuLV的ClaI-SmaI片段的相反重组病毒）一样有效。与 NwtTB-4（一种在 MoMuLV 背景下具有 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，趋胸性并不是决定 MoMuLV 诱导 T 细胞淋巴瘤潜力的唯一因素。一个或多个 MoMuLV-TB 核因子结合基序的突变似乎可能改变了增强子与特定核因子的相互作用；这反过来可能会影响 MoMuLV-TB 诱导 T 细胞淋巴瘤的潜力。
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.