Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication
Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication
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DOI：
10.1074/jbc.m501378200
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发表时间：
2005-07-08
影响因子：
4.8
通讯作者：
Benarous, R
中科院分区：
文献类型：
--
作者：
Emiliani, S;Mousnier, A;Benarous, R
其RNA基因组的DNA拷贝插入宿主细胞的染色体中由病毒整合酶在大多数未表征的细胞辅因子的帮助下介导。我们最近描述了转录共激活因子LEDGF/p75与HIV-1整合酶强烈相互作用。在这里，我们表明HIV-1整合酶与LEDGF/p75的相互作用对病毒复制很重要。使用多种方法，包括双杂交相互作用研究，随机和定向诱变，我们可以证明，HIV-1病毒携带一个单一的突变，破坏整合酶LEDGF/p75的相互作用，导致缺陷的HIV-1复制。此外，我们发现LEDGF/p75将HIV-1整合酶拴在染色体上，这种相互作用可能对HIV-1的整合过程和复制很重要。
The insertion of a DNA copy of its RNA genome into a chromosome of the host cell is mediated by the viral integrase with the help of mostly uncharacterized cellular cofactors. We have recently described that the transcriptional co-activator LEDGF/p75 strongly interacts with HIV-1 integrase. Here we show that interaction of HIV-1 integrase with LEDGF/p75 is important for viral replication. Using multiple approaches including two-hybrid interaction studies, random and directed mutagenesis, we could demonstrate that HIV-1 virus harboring a single mutation that disrupts integraseLEDGF/p75 interaction, resulted in defective HIV-1 replication. Furthermore, we found that LEDGF/p75 tethers HIV-1 integrase to chromosomes and that this interaction may be important for the integration process and the replication of HIV-1.