Document 3305
 DOCN  M94A3305
 TI    The C-terminal domain of HIV-1 Vpr causes cell growth arrest and
       structural defects.
 DT    9412
 AU    Macreadie I; Castelli L; Hewish D; Ward A; Azad A; Biomolecular Research
       Institute, Melbourne, Australia.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):106 (abstract no. PA0044). Unique
       Identifier : AIDSLINE ICA10/94369270
 AB    OBJECTIVE: To determine possible role of HIV-1 Vpr, a virion-associated
       accessory protein, in AIDS pathogenesis. METHODS: Full length and
       truncated vpr genes were expressed in yeast and the effects of
       expression on cell growth and morphology was studied. The effects of
       electroporation of synthetic C-terminal peptides of vpr into yeast cells
       was also studied. RESULTS: When expressed in yeast the HIV-1 vpr gene
       causes cell growth arrest and gross cell enlargement. The C-terminal 33
       amino acids of Vpr alone is responsible for this effect. This region
       contains a repeated HS/FRIG motif that is conserved in Vpr molecules
       from HIV-1, HIV-2 and SIVmac. C-terminal synthetic peptides containing
       this motif, when introduced into yeast cells by electroporation cause
       profound structural changes and loss of viability, while a shorter
       C-terminal peptide lacking this motif has no effect. DISCUSSION AND
       CONCLUSIONS: The C-terminal cytostatic domain of Vpr shows sequence
       similarity to Sac1p, a protein with functions relating to the yeast
       actin cytoskeleton; sac1 mutants display profound cytoskeleted defects
       and growth arrest. Due to sequence (and perhaps functional) similarity,
       Vpr could competitively inhibit normal Sac1p function leading to
       cytoskeleted changes and growth arrest. The cytostatic effect of Vpr is
       not peculiar to yeast cells as Levy et al. (Cell, 72, 541, 1993) have
       shown that vpr gene causes gross cell enlargement and replication arrest
       in a rhabdosarcoma (muscle) cell line. It would be interesting to see if
       virion-associated Vpr causes a similar effect in HIV-infected cells and
       if this phenomenon is important for some early event in infection.
 DE    Acquired Immunodeficiency Syndrome/ETIOLOGY  Amino Acid Sequence  Cell
       Division  Cell Line  Cytoskeleton/PATHOLOGY  Fungal Proteins/GENETICS
       Gene Expression  Gene Products, vpr/GENETICS/PHARMACOLOGY  *Genes, vpr
       Human  HIV-1/*GENETICS/PATHOGENICITY  Membrane Proteins/GENETICS
       Molecular Sequence Data  Peptide Fragments/GENETICS/PHARMACOLOGY
       Saccharomyces cerevisiae/GENETICS  Sequence Homology, Amino Acid
       MEETING ABSTRACT

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