       Document 0661
 DOCN  M9640661
 TI    Role of the karyopherin pathway in human immunodeficiency virus type 1
       nuclear import.
 DT    9604
 AU    Gallay P; Stitt V; Mundy C; Oettinger M; Trono D; Infectious Disease
       Laboratory, Salk Institute for Biological; Studies, La Jolla, California
       92037, USA.
 SO    J Virol. 1996 Feb;70(2):1027-32. Unique Identifier : AIDSLINE
       MED/96135215
 AB    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.
 DE    Amino Acid Sequence  Animal  Base Sequence  Carrier Proteins/*METABOLISM
       Cell Line  Cell Nucleus/METABOLISM/*VIROLOGY  DNA Primers  Gene
       Products, vpr/METABOLISM  Human  HIV-1/*METABOLISM  Molecular Sequence
       Data  Nucleoproteins/METABOLISM  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  Viral Matrix Proteins/*METABOLISM  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

