HIV-1 nuclear import: in search of a leader

The ability of HIV-1 to use host cell nuclear import machinery to translocate the viral pre-integration 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 pre-integration 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 pre-integration complex. Interestingly, some cells, in particular HeLa, seem to contain a factor that 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 that target the NLSs of HIV-1 and effectively block viral replication in T cells and macrophages.