McGill AIDS Center, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal QC, Canada H3T 1E2.
Virology. 2010 Nov 25;407(2):225-36. doi: 10.1016/j.virol.2010.08.013. Epub 2010 Sep 9.
Formation of immature genomic RNA (gRNA) dimers is exquisitely nucleocapsid (NC)-dependent in protease-inactive (PR-in) HIV-1. This establishes that Pr55gag/Pr160gag-pol has NC-dependent chaperone activity within intact HIV-1. Mutations in the proximal zinc finger and the linker of the NC sequence of Pr55gag/Pr160gag-pol abolish gRNA dimerization in PR-in HIV-1. In wild type, where the NC of Pr55gag is processed into progressively smaller proteins termed NCp15 (NCp7-p1-p6), NCp9 (NCp7-p1) and NCp7, formation of immature dimers is much swifter than in PR-in HIV-1. NCp7 and NCp15 direct this rapid accumulation. NCp9 is sluggish in this process, but it stimulates the transition from immature to mature gRNA dimer as well as NCp7 and much better than NCp15. The amino-terminus, proximal zinc finger, linker, and distal zinc finger of NCp7 contribute to this maturation event in intact HIV-1. The DIS is a dimerization initiation site for all immature gRNA dimers, irrespective of their mechanism of formation.
不成熟基因组 RNA (gRNA) 二聚体的形成在无蛋白酶活性（PR-in）的 HIV-1 中高度依赖核衣壳（NC）。这表明 Pr55gag/Pr160gag-pol 在完整的 HIV-1 内具有依赖 NC 的伴侣活性。Pr55gag/Pr160gag-pol 的 NC 序列近端锌指和连接子中的突变会在 PR-in HIV-1 中消除 gRNA 二聚体的形成。在野生型中，Pr55gag 的 NC 被加工成逐渐较小的蛋白，称为 NCp15（NCp7-p1-p6）、NCp9（NCp7-p1）和 NCp7，不成熟二聚体的形成速度比 PR-in HIV-1 快得多。NCp7 和 NCp15 指导这种快速积累。NCp9 在这个过程中比较缓慢，但它可以刺激从不成熟到成熟 gRNA 二聚体的转变，其作用比 NCp15 更好。NCp7 的氨基末端、近端锌指、连接子和远端锌指有助于完整 HIV-1 中的这一成熟事件。DIS 是所有不成熟 gRNA 二聚体的二聚化起始位点，无论其形成机制如何。
