Document 0600
 DOCN  M9550600
 TI    Use of a human immunodeficiency virus type 1 Rev mutant without
       nucleolar dysfunction as a candidate for potential AIDS therapy.
 DT    9505
 AU    Furuta RA; Kubota S; Maki M; Miyazaki Y; Hattori T; Hatanaka M;
       Department of Molecular Virology, Kyoto University, Japan.
 SO    J Virol. 1995 Mar;69(3):1591-9. Unique Identifier : AIDSLINE
       MED/95156585
 AB    Applications of transdominant mutants of human immunodeficiency virus
       type 1 (HIV-1) regulatory proteins, especially Rev mutant, have been
       attempted for gene therapy against AIDS, because the Rev protein is
       essential for viral replication. We have previously reported that a
       mutant Rev protein (dRev) lacking its nucleolar targeting signal
       remained out of nuclei in expressed cells and strongly inhibited the
       function of Rev. To investigate the effects of dRev on HIV-1
       replication, we established several dRev-expressing human cell lines
       with two different vector systems and examined virus production in these
       cells. An HIV-1-derived vector containing drev cDNA was constructed and
       introduced into CD4-positive HeLa cells and cells of the human T-cell
       line CCRF-CEM (CEM). In dRev-expressing HeLa cells, virus replication,
       syncytium formation, and cell death caused by HIV-1 infection were
       remarkably suppressed, and the same vector also conferred a resistant
       phenotype on CEM cells. The production was also suppressed in CEM cells
       containing the drev gene driven by a cytomegalovirus promoter. In
       addition, we found that dRev did not cause nucleolar dysfunction in a
       transient assay, in contrast to other transdominant mutants and
       wild-type Rev. Since dRev cannot migrate into the nuclei, it is expected
       not to interfere with nuclear/nucleolar functions of the host cell. We
       conclude that dRev is one promising candidate as an antiviral molecule
       for gene therapy against AIDS.
 DE    Acquired Immunodeficiency Syndrome/*THERAPY  Amino Acid Sequence  Base
       Sequence  Cell Line  Cell Nucleolus/PATHOLOGY  DNA Primers/CHEMISTRY
       Gene Expression Regulation, Viral  Gene Therapy  *Genes, rev  Genes,
       Dominant  Hela Cells  Human  HIV-1/GROWTH & DEVELOPMENT/*GENETICS
       Molecular Sequence Data  Mutation  RNA, Viral/GENETICS  Support,
       Non-U.S. Gov't  Virus Replication  JOURNAL ARTICLE

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