Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import

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J. Virol., Feb 1996, 1027-1032, Vol 70, No. 2
Copyright © 1996, American Society for Microbiology

Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import

P Gallay, V Stitt, C Mundy, M Oettinger and D Trono
Infectious Disease Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.

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.

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