       Document 3312
 DOCN  M94A3312
 TI    A new method of selecting HIV inhibitor in vitro.
 DT    9412
 AU    Cai C; Koga Y; Nomoto K; Medical Institute of Bioregulation, Kyushu
       University, Fukuoka,; Japan.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):105 (abstract no. PA0038). Unique
       Identifier : AIDSLINE ICA10/94369263
 AB    OBJECTIVE: A safe and rapid method of selecting HIV inhibitor in vitro
       is necessary for AIDS research and therapy. We established the method on
       HIV-1 env gene expression cell lines. METHODS: Human CD4+ T and
       monocytoid cell lines were transferred with HIV-1 env gene expression
       vector in which the activity of the promotor could be augmented 10-20
       times by heavy ions. Each cell population adjusted to 100,000 cells in 1
       ml RPMI 1640 medium containing 0 or 20 microM cadmium chloride was
       cultured with dextran sulphate (MW 5,000, 0 or 100 micrograms/ml),
       mitomycin (0 or 1 ng/ml), alpha-amanitin (0 or 1 microgram/ml) or
       cycloheximide (0 or 1 microgram/ml) respectively. The cell numbers were
       determined every second day. RESULTS: When the expression of HIV-1 env
       gene was induced by heavy ions, the cell line derived from CD4+ T cell
       showed extensive cytopathic effects, such as syncytium formation (12,000
       giant cells/ml/day 6) and cell death (a 49.8% cell death in a total of
       2,170,000 cells/ml/day 6); the cell line derived from CD4+ monocytoid
       cell also showed cell death (a 528% cell death in a total of 2,180,000
       cells/ml/day 6) but syncytium formation. After dextran sulphate was
       administered, both cell lines showed no syncytium formation and low
       death rates (a 0.9% cell death in the total of 2,170,000 T cells/ml/day
       6; a 5.0% cell death in the total of 2,180,000 monocytoid cells/ml/day
       6). The administrations of mitomycin, alpha--amanitin or cycloheximide
       failed to show any significant cytopathic inhibitory effects. DISCUSSION
       AND CONCLUSIONS: Dextran sulphate blocks the cell fusion and protects
       the cell from death on HIV-1 env gene expressing CD4+ T and monocytiod
       cells. The method is recommendable as a safe and rapid method of
       selecting HIV inhibitor in vitro.
 DE    Antiviral Agents/*PHARMACOLOGY  Cell Death/DRUG EFFECTS  Cell
       Fusion/DRUG EFFECTS  Cell Line  Cytopathogenic Effect, Viral/DRUG
       EFFECTS  Dextran Sulfate/PHARMACOLOGY  Drug Screening/*METHODS  Gene
       Expression/DRUG EFFECTS  Genes, env/DRUG EFFECTS  Human  HIV-1/*DRUG
       EFFECTS/GENETICS/PATHOGENICITY  Monocytes/DRUG EFFECTS/MICROBIOLOGY  T4
       Lymphocytes/DRUG EFFECTS/MICROBIOLOGY  MEETING ABSTRACT

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

