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 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.
Bukrinsky
M I
MI
The Picower Institute for Medical Research, Manhasset, NY 11030, USA. mbukrinsky@picower.edu
Haffar
O K
OK
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D019380:Anti-HIV Agents / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019913:Nuclear Localization Signals / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D028901:alpha Karyopherins / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000378:metabolism
D019380:Anti-HIV Agents; D019913:Nuclear Localization Signals; D014764:Viral Proteins; D028901:alpha Karyopherins; D020931:ran GTP-Binding Protein