Polyomavirus tumor induction in mice: influences of viral coding and noncoding sequences on tumor profiles.
Polyomavirus tumor induction in mice: influences of viral coding and noncoding sequences on tumor profiles.
复制标题
小鼠多瘤病毒肿瘤诱导：病毒编码和非编码序列对肿瘤特征的影响。
DOI：
10.1128/jvi.61.7.2232-2239.1987
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发表时间：
1987
影响因子：
5.4
通讯作者：
Benjamin,TL
中科院分区：
文献类型：
--
作者：
Freund,R;Mandel,G;Carmichael,GG;Barncastle,JP;Dawe,CJ;Benjamin,TL
我们确定了两种多瘤病毒株非编码区的 DNA 序列，这两种病毒株诱导小鼠肿瘤的能力差异很大。在含有已知增强子元件的区域的复制起点的后侧和起点的早期侧都发现了菌株之间的差异，影响了大T抗原结合位点的数量和位置。通过构建和分析这些高肿瘤株和低肿瘤株之间的重组病毒，我们试图定位影响肿瘤频率和组织型的决定因素。构建了七个重组体并在体外进行增殖，并且通过接种新生 C3H 小鼠来建立每个重组体的肿瘤特征。含有来自高肿瘤菌株的非编码序列和来自低肿瘤菌株的编码序列的重组体表现得与后者相似，以低频率诱导肿瘤并且严格具有间质来源。低肿瘤株的非编码序列与高肿瘤株的结构决定簇连接的相互重组体除了间充质肿瘤外，还诱导了高肿瘤株典型的几种类型的上皮肿瘤，但频率降低。需要高频率和完全多样性的上皮肿瘤，除了高肿瘤菌株的结构区域之外，起源早期侧的非编码序列也存在于该菌株中。因此，高肿瘤特征是高肿瘤菌株中结构和调节决定因素的综合作用的结果，前者主要影响组织向性，后者影响肿瘤的频率。本研究中未发现两种病毒株起源后侧的增强子区域存在差异效应。
We determined the DNA sequences of the noncoding regions of two polyomavirus strains that differ profoundly in their abilities to induce tumors in mice. Differences between strains were found, both on the late side of the replication origin in the region containing known enhancer elements and on the early side of the origin, affecting the number and location of large-T-antigen-binding sites. By constructing and analyzing recombinant viruses between these high- and low-tumor strains, we attempted to localize determinants which affect the frequency and histotype of tumors. Seven recombinants were constructed and propagated in vitro, and the tumor profile of each was established by inoculation into newborn C3H mice. Recombinants containing noncoding sequences from the high-tumor strain and coding sequences from the low-tumor strain behaved like the latter, inducing tumors at a low frequency and strictly of mesenchymal origin. Reciprocal recombinants with noncoding sequences of the low-tumor strain linked to structural determinants from the high-tumor strain induced several types of epithelial tumors typical of the high-tumor strain but at reduced frequency, in addition to mesenchymal tumors. A high frequency and full diversity of epithelial tumors required, in addition to structural regions from the high-tumor strain, noncoding sequences on the early side of the origin also present in this strain. A high-tumor profile thus resulted from the combined effects of structural and regulatory determinants in the high-tumor strain, with the former affecting primarily the tissue tropism and the latter affecting the frequency of tumors. No differential effects of the enhancer regions from the late side of the origin in the two virus strains were seen in this study.