Ariumi Yasuo, Serhan Fatima, Turelli Priscilla, Telenti Amalio, Trono Didier
Department of Microbiology and Molecular Medicine, University of Geneva and Frontiers in Genetics National Center for Competence in Research, Switzerland.
Retrovirology. 2006 Aug 5;3:47. doi: 10.1186/1742-4690-3-47.
Integration of human immunodeficiency virus type 1 (HIV-1) into the host genome is catalyzed by the viral integrase (IN) and preferentially occurs within transcriptionally active genes. During the early phase of HIV-1 infection, the incoming viral preintegration complex (PIC) recruits the integrase interactor 1 (INI1)/hSNF5, a chromatin remodeling factor which directly binds to HIV-1 IN. The impact of this event on viral replication is so far unknown, although it has been hypothesized that it could tether the preintegration complex to transcriptionally active genes, thus contributing to the bias of HIV integration for these regions of the genome. Here, we demonstrate that while INI1 is dispensable for HIV-1 transduction, it can facilitate HIV-1 transcription by enhancing Tat function. INI1 bound to Tat and both the repeat (Rpt) 1 and Rpt 2 domains of INI1 were required for efficient activation of Tat-mediated transcription. These results suggest that the incoming PICs might recruit INI1 to facilitate proviral transcription.
1型人类免疫缺陷病毒(HIV-1)整合至宿主基因组是由病毒整合酶(IN)催化的,且优先发生在转录活跃基因内。在HIV-1感染的早期阶段,进入的病毒前整合复合物(PIC)招募整合酶相互作用因子1(INI1)/hSNF5,这是一种染色质重塑因子,可直接与HIV-1 IN结合。尽管有人推测这一事件可能会将前整合复合物拴系至转录活跃基因,从而导致HIV整合偏向于基因组的这些区域,但到目前为止,该事件对病毒复制的影响尚不清楚。在此,我们证明,虽然INI1对于HIV-1转导并非必需,但它可以通过增强Tat功能来促进HIV-1转录。INI1与Tat结合,并且INI1的重复(Rpt)1和Rpt 2结构域对于Tat介导的转录的有效激活都是必需的。这些结果表明,进入的PIC可能会招募INI1以促进前病毒转录。