Document 0397
 DOCN  M9460397
 TI    Assembly and extracellular release of chimeric HIV-1 Pr55gag
       retrovirus-like particles.
 DT    9404
 AU    Wagner R; Deml L; Fliessbach H; Wanner G; Wolf H; Institut fur med.
       Mikrobiologie, LMU-Munchen, Federal Republic; of Germany.
 SO    Virology. 1994 Apr;200(1):162-75. Unique Identifier : AIDSLINE
       MED/94174714
 AB    The HIV-1 Pr55gag precursors were previously shown to assemble and bud
       from a variety of different cell types as noninfectious virus-like
       particles (VLPs) resembling immature HIV virions. The use of these VLPs
       as an immunogenic and autologous carrier component may allow the
       presentation of defined epitopes deduced from reading frames other than
       gag to the immune system, thereby avoiding the induction of adverse
       immune responses. In order to identify domains within Pr55gag that can
       be replaced by immunologically relevant epitopes without affecting its
       capacity to assemble into VLPs, we deleted three domains of a predicted
       high surface probability. Deletion of amino acids 211-241 within p24CA
       and amino acids 436-471 within the p6LI portion of Pr55gag had no effect
       on the assembly, ultrastructure, biophysical properties, and yields of
       mutant VLPs when expressed via recombinant vaccinia viruses in mammalian
       cells. Deletion of amino acids 99-154 overlapping the p17MA/p24CA
       cleavage site completely abolished the capacity of the gag polyprotein
       to form VLPs and led to a reduction of immature Pr55 VLPs released into
       the cell-culture supernatants when coexpressed with wild-type Pr55gag.
       In contrast, assembly and budding of chimeric VLPs could be demonstrated
       after replacing amino acids 211-241 and 436-471 by immunologically
       relevant epitopes derived from reading frames other than Pr55gag (e.g.,
       V3 loop; CD4-binding-domain; nef-CTL epitope) or after fusion of these
       sequences to the carboxy terminus of Pr55gag. The importance of these
       data for the development of novel HIV candidate vaccines is discussed.
 DE    Amino Acid Sequence  Antigenic
       Determinants/GENETICS/IMMUNOLOGY/*METABOLISM  Base Sequence  Chimeric
       Proteins/GENETICS/IMMUNOLOGY/*METABOLISM  DNA Mutational Analysis  Gene
       Products, gag/GENETICS/IMMUNOLOGY/*METABOLISM  HIV Envelope Protein
       gp120/GENETICS/IMMUNOLOGY  HIV-1/*GROWTH &
       DEVELOPMENT/GENETICS/IMMUNOLOGY/ULTRASTRUCTURE  Molecular Sequence Data
       Mutation  Protein Precursors/GENETICS/IMMUNOLOGY/*METABOLISM  Support,
       Non-U.S. Gov't  Vaccinia Virus/GENETICS/ULTRASTRUCTURE  Virion/*GROWTH &
       DEVELOPMENT/GENETICS/IMMUNOLOGY/ULTRASTRUCTURE  JOURNAL ARTICLE

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