Influence of enhancer sequences on thymotropism and leukemogenicity of mink cell focus-forming viruses.
Influence of enhancer sequences on thymotropism and leukemogenicity of mink cell focus-forming viruses.
复制标题
增强子序列对水貂细胞病灶形成病毒的趋胸性和致白血病性的影响。
DOI：
10.1128/jvi.63.3.1284-1292.1989
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发表时间：
1989
影响因子：
5.4
通讯作者：
O'Donnell,PV
中科院分区：
文献类型：
--
作者：
Holland,CA;Thomas,CY;Chattopadhyay,SK;Koehne,C;O'Donnell,PV
致瘤水貂细胞灶形成（MCF）病毒，如MCF 247，显示出在胸腺中有效复制的能力与致白血病表型之间的正相关性。其他MCF病毒，如MCF 30-2，在胸腺细胞中复制到高滴度，不会加速白血病的发生。我们使用这两种具有不同生物学表型的MCF病毒来区分特定病毒基因和遗传决定簇对胸腺向性和致白血病性的影响。我们的目标是确定病毒序列，区分胸腺，非白血病病毒，如MCF 30-2从胸腺，白血病病毒，如MCF 247。我们克隆了MCF 30-2，比较了MCF 30-2与MCF 247的遗传标志，构建了一系列重组体，并测试了重组病毒在胸腺中复制和诱导白血病的能力。结果确定：（i）MCF 30-2和MCF 247在长末端重复序列中增强子序列的拷贝数上不同。(ii)这两种病毒的亲胸腺表型与增强子序列的拷贝数无关。(iii)MCF 247的致癌表型与病毒中存在重复的增强子序列或存在具有特定序列的增强子相关。这些结果表明，MCF病毒的致病性表型是可分离的胸腺表型，并依赖于，至少部分地，在增强子序列。基于这些结果，我们认为增强子序列决定胸腺性的分子机制不同于决定致癌性的分子机制。
Oncogenic mink cell focus-forming (MCF) viruses, such as MCF 247, show a positive correlation between the ability to replicate efficiently in the thymus and a leukemogenic phenotype. Other MCF viruses, such as MCF 30-2, replicate to high titers in thymocytes and do not accelerate the onset of leukemia. We used these two MCF viruses with different biological phenotypes to distinguish the effect of specific viral genes and genetic determinants on thymotropism and leukemogenicity. Our goal was to identify the viral sequences that distinguish thymotropic, nonleukemogenic viruses such as MCF 30-2 from thymotropic, leukemogenic viruses such as MCF 247. We cloned MCF 30-2, compared the genetic hallmarks of MCF 30-2 with those of MCF 247, constructed a series of recombinants, and tested the ability of recombinant viruses to replicate in the thymus and to induce leukemia. The results established that (i) MCF 30-2 and MCF 247 differ in the numbers of copies of the enhancer sequences in the long terminal repeats. (ii) The thymotropic phenotype of both viruses is independent of the number of copies of the enhancer sequences. (iii) The oncogenic phenotype of MCF 247 is correlated with the presence in the virus of duplicated enhancer sequences or with the presence of an enhancer with a specific sequence. These results show that the pathogenic phenotypes of MCF viruses are dissociable from the thymotropic phenotype and depend, at least in part, upon the enhancer sequences. On the basis of these results, we suggest that the molecular mechanisms by which the enhancer sequences determine thymotropism are different from those that determine oncogenicity.