Bukrinsky M I, Haffar O K
The Picower Institute for Medical Research, Manhasset, NY 11030, USA.
Front Biosci. 1997 Dec 1;2:d578-87. doi: 10.2741/a213.
The ability of HIV-1 to use host cell nuclear import machinery to translocate the viral preintegration complex into the cell nucleus is the critical determinant in the replication of the virus in non-dividing cells, such as macrophages. In this review, we describe the viral and cellular factors involved in this process. The available data suggest that the process of HIV-1 nuclear import is driven by interaction between nuclear localization signals (NLSs) present on viral proteins matrix and integrase and the cellular NLS receptor, karyopherin alpha. However, this interaction by itself is weak and insufficient to insure effective import of the preintegration complex. Viral protein R (Vpr) functions to increase the affinity of interaction between viral NLSs and karyopherin alpha, thus substantially enhancing the karyophilic potential of the preintegration complex. Interestingly, some cells, in particular HeLa, seem to contain a factor which can substitute for the Vpr's activity, making HIV-1 replication in such cells Vpr-independent. We also describe a class of novel anti-HIV compounds which target the NLSs of HIV-1 and effectively block viral replication in T cells and macrophages.
人类免疫缺陷病毒1型（HIV-1）利用宿主细胞核输入机制将病毒前整合复合物转运至细胞核的能力，是该病毒在非分裂细胞（如巨噬细胞）中复制的关键决定因素。在本综述中，我们描述了参与这一过程的病毒和细胞因子。现有数据表明，HIV-1核输入过程是由病毒蛋白基质和整合酶上存在的核定位信号（NLSs）与细胞NLS受体核转运蛋白α之间的相互作用驱动的。然而，这种相互作用本身较弱，不足以确保前整合复合物的有效输入。病毒蛋白R（Vpr）的作用是增加病毒NLSs与核转运蛋白α之间相互作用的亲和力，从而显著增强前整合复合物的亲核潜力。有趣的是，一些细胞，特别是HeLa细胞，似乎含有一种可以替代Vpr活性的因子，使得HIV-1在此类细胞中的复制不依赖Vpr。我们还描述了一类新型抗HIV化合物，它们靶向HIV-1的NLSs，并有效阻断病毒在T细胞和巨噬细胞中的复制。
