人类免疫缺陷病毒1型（HIV-1）整合进人类基因组时倾向于活跃基因和局部热点区域。

HIV-1 integration in the human genome favors active genes and local hotspots.

作者信息

Schröder Astrid R W, Shinn Paul, Chen Huaming, Berry Charles, Ecker Joseph R, Bushman Frederic

机构信息

Infectious Disease Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.

出版信息

Cell. 2002 Aug 23;110(4):521-9. doi: 10.1016/s0092-8674(02)00864-4.

DOI:10.1016/s0092-8674(02)00864-4

PMID:12202041

Abstract

A defining feature of HIV replication is integration of the proviral cDNA into human DNA. The selection of chromosomal targets for integration is crucial for efficient viral replication, but the mechanism is poorly understood. Here we describe mapping of 524 sites of HIV cDNA integration on the human genome sequence. Genes were found to be strongly favored as integration acceptor sites. Global analysis of cellular transcription indicated that active genes were preferential integration targets, particularly genes that were activated in cells after infection by HIV-1. Regional hotspots for integration were also found, including a 2.4 kb region containing 1% of sites. These data document unexpectedly strong biases in integration site selection and suggest how selective targeting promotes aggressive HIV replication.

摘要

HIV复制的一个决定性特征是前病毒cDNA整合到人类DNA中。选择用于整合的染色体靶点对于病毒的高效复制至关重要，但其机制尚不清楚。在此，我们描述了HIV cDNA在人类基因组序列上524个整合位点的定位。研究发现基因作为整合受体位点受到强烈青睐。对细胞转录的整体分析表明，活跃基因是优先的整合靶点，尤其是在HIV-1感染后细胞中被激活的基因。还发现了整合的区域热点，包括一个包含1%位点的2.4 kb区域。这些数据表明整合位点选择存在出人意料的强烈偏向性，并揭示了选择性靶向如何促进HIV的侵袭性复制。