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).