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M9640661.TXT
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1996-03-04
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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).