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1994-08-27
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44 lines
Document 0699
DOCN M9480699
TI The Vpr protein of human immunodeficiency virus type 1 influences
nuclear localization of viral nucleic acids in nondividing host cells.
DT 9410
AU Heinzinger NK; Bukinsky MI; Haggerty SA; Ragland AM; Kewalramani V; Lee
MA; Gendelman HE; Ratner L; Stevenson M; Emerman M; Department of
Pathology and Microbiology, University of Nebraska; Medical Center,
Omaha 68198-5120.
SO Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7311-5. Unique Identifier :
AIDSLINE MED/94316685
AB The replication of human immunodeficiency virus type 1 (HIV-1) in
nondividing host cells such as those of macrophage lineage is an
important feature of AIDS pathogenesis. The pattern of HIV-1 replication
is dictated, in part, by the nucleophilic property of the viral gag
matrix (MA) protein, a component of the viral preintegration complex
that facilitates nuclear localization of viral nucleic acids in the
absence of mitosis. We now identify the accessory viral protein Vpr, as
a second nucleophilic component that influences nuclear localization of
viral nucleic acids in nondividing cells. Reverse transcription and
nuclear localization of viral nucleic acids following infection of cells
by viruses lacking Vpr or viruses containing mutations in a gag MA
nuclear localization sequence were indistinguishable from the pattern
observed in cells infected by wild-type HIV-1. These viruses retained
the ability to replicate in both dividing and nondividing host cells
including monocyte-derived macrophages. In contrast, introduction of
both gag MA and Vpr mutations in HIV-1 attenuated nuclear localization
of viral nucleic acids in nondividing cells and virus replication in
monocyte-derived macrophages. These studies demonstrate redundant
nucleophilic determinants of HIV-1 that independently permit nuclear
localization of viral nucleic acids and virus replication in nondividing
cells such as monocyte-derived macrophages. In addition, these studies
provide a defined function for an accessory gene product of HIV-1.
DE Base Sequence Cell Division Cell Line Cell Nucleus/METABOLISM
Cloning, Molecular DNA, Viral/BIOSYNTHESIS/*METABOLISM Gene Products,
vpr/*METABOLISM Human HIV-1/GENETICS/*METABOLISM Molecular Sequence
Data Mutation Polymerase Chain Reaction Support, Non-U.S. Gov't
Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. JOURNAL
ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).