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).