Swain A, Coffin J M
Tufts University School of Medicine, Department of Molecular Biology and Microbiology, Boston, MA 02111.
Science. 1992 Feb 14;255(5046):841-5. doi: 10.1126/science.1371365.
Retroviruses can capture cellular sequences and express them as oncogenes. Capture has been proposed to be a consequence of the inefficiency of polyadenylation of the viral genome that allows the packaging of cellular sequences flanking the integrated provirus in virions; after transfer into virions, these sequences could be incorporated into the viral genome by illegitimate recombination during reverse transcription. As a test for this hypothesis, a tissue culture system was developed that mimics the transduction process and allows the analysis and quantitation of capture events in a single step. In this model, transduction of sequences adjacent to a provirus depends on the formation of readthrough transcripts and their transmission in virions and leads to various recombinant structures whose formation is independent of sequence similarity at the crossover site. Thus, all events in the transduction process can be attributed to the action of reverse transcriptase on readthrough transcripts without involving deletions of cellular DNA.
逆转录病毒能够捕获细胞序列并将其作为癌基因表达。捕获现象被认为是病毒基因组聚腺苷酸化效率低下的结果,这种低效率使得整合的前病毒侧翼的细胞序列能够被包装进病毒粒子中;在转移到病毒粒子后,这些序列可能在逆转录过程中通过非法重组被整合到病毒基因组中。作为对这一假说的验证,开发了一种组织培养系统,该系统模拟转导过程,并允许在一步中分析和定量捕获事件。在这个模型中,前病毒相邻序列的转导取决于通读转录本的形成及其在病毒粒子中的传递,并导致各种重组结构的形成,这些重组结构的形成与交叉位点处的序列相似性无关。因此,转导过程中的所有事件都可归因于逆转录酶对通读转录本的作用,而不涉及细胞DNA的缺失。