MECHANISM OF TRANSDUCTION BY RETROVIRUSES

MECHANISM OF TRANSDUCTION BY RETROVIRUSES
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DOI:
10.1126/science.1371365
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发表时间:
1992-02-14
期刊:
影响因子:
56.9
通讯作者:
COFFIN, JM
COFFIN, JM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
SWAIN, A;COFFIN, JM

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逆转录病毒可以捕获细胞序列并将其表达为癌基因。已经提出捕获是病毒基因组的多聚腺苷酸化效率低下的结果,其允许病毒体中整合的前病毒侧翼的细胞序列的包装;在转移到病毒体中之后,这些序列可以通过逆转录期间的非法重组并入病毒基因组中。作为对该假设的测试,开发了模拟转导过程并允许在单个步骤中分析和定量捕获事件的组织培养系统。在该模型中,与前病毒相邻的序列的转导依赖于通读转录物的形成及其在病毒体中的传递,并导致各种重组结构,其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以归因于逆转录酶对通读转录物的作用,而不涉及细胞DNA的缺失。
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.