       Document 0386
 DOCN  M9590386
 TI    The C-terminal domain of HIV-1 Vpr causes cell growth arrest and
       structural defects.
 DT    9509
 AU    Azad A; Arunagiri C; Hewish D; Macreadie I; Biomolecular Research
       Institute, Parkville, Victoria.
 SO    Annu Conf Australas Soc HIV Med. 1994 Nov 3-6;6:102 (unnumbered
       abstract). Unique Identifier : AIDSLINE ASHM6/95291713
 AB    OBJECTIVE: To determine the possible role of Vpr in AIDS pathogenesis by
       studying its effects on host cells. METHODOLOGY: Full length and
       truncated vpr genes were expressed in yeast cells and the effects of
       expression on cell growth, morphology and viability was studied. The
       effects of electroporation of synthetic C-terminal peptides of Vpr into
       yeast cells and human CD4+ cells was also studied. RESULTS: The
       synthesis of Vpr in yeast causes cell growth arrest and gross cell
       enlargement. Expression of truncated forms of Vpr shows that growth
       arrest in yeast is caused by the C-terminal third of Vpr and implicates
       the sequence HFRIGCRHSRIG. Electroporation of yeast cells with
       C-terminal peptides shows that peptides containing the HS/FRIG motifs
       cause structural defects that result in osmotic sensitivity.
       Electroporation of the C-terminal peptides containing the HS/FRIG motifs
       into human CD4+ cells causes enlargement of the cell and the nucleus,
       and causes increased cell death. Comparison of Vpr sequences from HIV-1,
       HIV-2 and SIV shows a correlation between the conservation of the
       HS/FRIG motifs and pathogenicity of primate lentiviruses. CONCLUSION:
       The function Vpr may be to bring about cell growth arrest and/or
       cytoskeletal changes to facilitate early events in HIV infection.
 DE    Cell Division/*GENETICS  Cell Line  Cell Transformation, Viral/*GENETICS
       CD4-Positive T-Lymphocytes/VIROLOGY  Electroporation  Genes,
       vpr/*GENETICS  Human  HIV-1/*GENETICS  HIV-2/GENETICS  Peptide
       Fragments/*GENETICS  Peptide Termination Factors/*GENETICS  SIV/GENETICS
       Virulence  Virus Replication/*GENETICS  Yeasts  MEETING ABSTRACT

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

