Characterization of HIV-1 vpr nuclear import: analysis of signals and pathways.
While the Vpr protein of HIV-1 has been implicated in import of the viral preintegration complex across the nuclear pore complex (NPC) of nondividing cellular hosts, the mechanism by which Vpr enters the nucleus remains unknown. We now demonstrate that Vpr contains two discrete nuclear targeting signals that use two different import pathways, both of which are distinct from the classical nuclear localization signal (NLS)- and the M9-dependent pathways. Vpr import does not appear to require Ran-mediated GTP hydrolysis and persists under conditions of low energy. Competition experiments further suggest that Vpr directly engages the NPC at two discrete sites. These sites appear to form distal components of a common import pathway used by NLS- and M9-containing proteins. Together, our data suggest that Vpr bypasses many of the soluble receptors involved in import of cellular cargoes. Rather, this viral protein appears to directly access the NPC, a property that may help to ensure the capacity of HIV to replicate in nondividing cellular hosts.
Jenkins
Y
Y
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94141-9100, USA.
McEntee
M
M
Weis
K
K
Greene
W C
WC
D001667:Binding, Competitive / Q000502:physiology; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D028884:Karyopherins; D007763:Lac Operon; D009685:Nuclear Envelope / Q000378:metabolism* / Q000821:virology; D019913:Nuclear Localization Signals / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D016662:Virus Integration / Q000502:physiology*; D020931:ran GTP-Binding Protein; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D028884:Karyopherins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D010446:Peptide Fragments; D054325:vpr Gene Products, Human Immunodeficiency Virus; D006160:Guanosine Triphosphate; D020931:ran GTP-Binding Protein