HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection.
HIV-1 Vpr promotes nuclear entry of viral nucleic acids in nondividing macrophages and also causes a G2 cell-cycle arrest. Consistent with its role in nuclear transport, we show Vpr localizes to the nuclear envelope in both human and yeast cells. Like the importin-beta subunit of the nuclear import receptor, Vpr also interacts with the yeast importin-alpha subunit and nucleoporins. Moreover, overexpression of either Vpr or importin-beta in yeast blocks nuclear transport of mRNAs. A mutant form of Vpr (Vpr F34I) that does not localize at the nuclear envelope, or bind to importin-alpha and nucleoporins, renders HIV-1 incapable of infecting macrophages efficiently. Vpr F34I, however, still causes a G2 arrest, demonstrating that the dual functions of Vpr are genetically separable. Our data suggest Vpr functionally resembles importin-beta in nuclear import of the HIV-1 pre-integration complex and this function is essential for the role of Vpr in macrophage infection, but not G2 arrest.
Vodicka
M A
MA
Divisions of Molecular Medicine and Basic Science, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 USA.
Koepp
D M
DM
Silver
P A
PA
Emerman
M
M
D002467:Cell Nucleus / Q000378:metabolism* / Q000821:virology; D002478:Cells, Cultured; D019084:Fluorescent Antibody Technique, Indirect; D016195:G2 Phase / Q000235:genetics; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000821:virology*; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D017354:Point Mutation; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000821:virology; D015003:Yeasts / Q000378:metabolism; D028901:alpha Karyopherins; D028961:beta Karyopherins; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D009687:Nuclear Proteins; D012333:RNA, Messenger; D028901:alpha Karyopherins; D028961:beta Karyopherins; D054325:vpr Gene Products, Human Immunodeficiency Virus