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1型人类免疫缺陷病毒链转移的性质

The nature of human immunodeficiency virus type 1 strand transfers.

作者信息

Yu H, Jetzt A E, Ron Y, Preston B D, Dougherty J P

机构信息

Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.

出版信息

J Biol Chem. 1998 Oct 23;273(43):28384-91. doi: 10.1074/jbc.273.43.28384.

Abstract

The diploid nature of human immunodeficiency virus type 1 (HIV-1) suggests that recombination serves a central function in virus replication and evolution. A system was developed to examine HIV-1 strand transfers, including the obligatory DNA primer strand transfers as well as recombinational crossovers during reverse transcription. Sequence heterogeneity between different strains of HIV-1 was exploited for examining primer transfer events. Both intra- and intermolecular primer transfers were observed at similar frequencies during minus-strand DNA synthesis, whereas primer transfers during plus-strand DNA synthesis were primarily intramolecular. Sequence analysis of long terminal repeats from progeny proviruses also revealed a high rate of homologous recombination during minus-strand synthesis, corresponding to an overall rate of approximately three crossovers per HIV-1 genome per cycle of replication. These results imply that both viral genomic RNAs serve as templates during HIV-1 reverse transcription and that primer strand transfers and recombination may contribute substantially to the rapid genetic variation of HIV-1.

摘要

人类免疫缺陷病毒1型(HIV-1)的二倍体性质表明,重组在病毒复制和进化中起着核心作用。我们开发了一个系统来检测HIV-1链转移,包括在逆转录过程中必不可少的DNA引物链转移以及重组交叉。利用不同HIV-1毒株之间的序列异质性来检测引物转移事件。在负链DNA合成过程中,分子内和分子间引物转移的频率相似,而正链DNA合成过程中的引物转移主要是分子内的。对子代前病毒长末端重复序列的序列分析也显示,在负链合成过程中同源重组率很高,相当于每个HIV-1基因组在每个复制周期中总体约有三次交叉。这些结果表明,在HIV-1逆转录过程中,两条病毒基因组RNA均作为模板,引物链转移和重组可能对HIV-1的快速基因变异有很大贡献。

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