Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import.
The interaction of the human immunodeficiency virus type 1 (HIV-1) nucleoprotein complex with the cell nuclear import machinery is necessary for viral replication in macrophages and for the establishment of infection in quiescent T lymphocytes. The karyophilic properties of two viral proteins, matrix (MA) and Vpr, are keys to this process. Here, we show that an early step of HIV-1 nuclear import is the recognition of the MA nuclear localization signal (NLS) by Rch1, a member of the karyopherin-alpha family. Furthermore, we demonstrate that an N-terminally truncated form of Rch1 which binds MA but fails to localize to the nucleus efficiently blocks MA- but not Vpr-mediated HIV-1 nuclear import. Correspondingly, NLS peptide inhibits the nuclear migration of MA but not that of Vpr and prevents the infection of terminally differentiated macrophages by vpr-defective virus but not wild-type virus. These results are consistent with a model in which Rch1 or another member of the karyopherin-alpha family, through the recognition of the MA NLS, participates in docking the HIV-1 nucleoprotein complex at the nuclear pore. In addition, our data suggest that Vpr governs HIV-1 nuclear import through a distinct pathway.
Gallay
P
P
Infectious Disease Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Stitt
V
V
Mundy
C
C
Oettinger
M
M
Trono
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology*; D017931:DNA Primers; D016336:Gene Products, vpr / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000378:metabolism*; D028901:alpha Karyopherins; D054325:vpr Gene Products, Human Immunodeficiency Virus
D002352:Carrier Proteins; D017931:DNA Primers; D016336:Gene Products, vpr; D009698:Nucleoproteins; D014763:Viral Matrix Proteins; D028901:alpha Karyopherins; C087978:karyopherin alpha 2; D054325:vpr Gene Products, Human Immunodeficiency Virus