Cochran M A, Mackett M, Moss B
Proc Natl Acad Sci U S A. 1985 Jan;82(1):19-23. doi: 10.1073/pnas.82.1.19.
A transient expression system in which chimeric genes are expressed in cells infected with vaccinia virus was developed. Recombinant plasmids containing the promoter regions of vaccinia virus genes ligated to the coding segment of the prokaryotic chloramphenicol acetyltransferase (CAT) gene were constructed. When the plasmids were introduced into vaccinia virus-infected cells by transfection, the chimeric gene was expressed and significant levels of CAT accumulated. CAT activity was not detected when the same recombinant plasmid was introduced into uninfected cells, nor was activity detected when the vaccinia virus promoter was absent from the plasmid or was replaced by simian virus 40 or Rous sarcoma virus promoters. This specificity indicated that expression is dependent on a cis-acting vaccinia virus promoter region within the recombinant plasmid and diffusible trans-acting transcription factors produced during virus infection. The lack of effect of a simian virus 40 enhancer element inserted upstream of the vaccinia virus promoter region also distinguished this system from systems dependent on RNA polymerase II. Although replication of the recombinant plasmid could not be detected in either uninfected or vaccinia virus-infected cells, an inhibitor of DNA synthesis significantly reduced CAT expression. This result, as well as the kinetics of CAT synthesis, suggests that replication of viral DNA templates can enhance transcription of chimeric genes in recombinant plasmids.
构建了一种瞬时表达系统,其中嵌合基因在感染痘苗病毒的细胞中表达。构建了重组质粒,其含有与原核氯霉素乙酰转移酶(CAT)基因编码片段连接的痘苗病毒基因启动子区域。当通过转染将质粒导入感染痘苗病毒的细胞时,嵌合基因表达,并且积累了显著水平的CAT。当将相同的重组质粒导入未感染的细胞时未检测到CAT活性,当质粒中不存在痘苗病毒启动子或被猴病毒40或劳斯肉瘤病毒启动子取代时也未检测到活性。这种特异性表明表达依赖于重组质粒内的顺式作用痘苗病毒启动子区域和病毒感染期间产生的可扩散反式作用转录因子。插入痘苗病毒启动子区域上游的猴病毒40增强子元件缺乏作用也使该系统与依赖RNA聚合酶II的系统区分开来。尽管在未感染或感染痘苗病毒的细胞中均未检测到重组质粒的复制,但DNA合成抑制剂显著降低了CAT表达。这一结果以及CAT合成的动力学表明,病毒DNA模板的复制可以增强重组质粒中嵌合基因的转录。