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Inhibition of Feline Immunodeficiency Virus Production and HIV Tat Activity by Thiosemicarbazone Derivatives

1994; SAGE Publishing; Volume: 5; Issue: 4 Linguagem: Inglês

10.1177/095632029400500404

2040-2066

Yael Teitz, Nir Barko, M Torten, D Ronen,

RNA Interference and Gene Delivery

Two thiosemicarbazone derivatives (TSCD), N-methylisatin-β-4′:4′-diethylthiosemicarbazone (M-IBDET) and N-allylisatin-β-4′:4-diallylthiosemicarbazone (A-IBDAT), were tested for their anti-feline immunodeficiency virus (FIV) activity in FL 4 /FIV cells. This cell line consists of feline T-lymphocytes chronically infected with FIV. FIV production in FL 4 /FIV cells was inhibited by M-IBDET and A-IBDAT. Virus inhibition was proportional to drug concentrations and time of treatment. The effective antiviral drug concentrations ranged from 0.06 to 0.64 μm for M-IBDET and from 0.45 to 8.7 μm for A-IBDAT. Tests performed to determine the therapeutic index (TI) value for each drug indicated TI values of 10 and 20 for M-IBDET and A-IBDAT, respectively. Continuous treatment of the cells with low doses of the drugs, given at constant time intervals, for a whole month succeeded in suppressing the chronic infection. Experiments directed towards understanding the mode of inhibition of FIV by TSCD indicated that A-IBDAT is involved in repression of the synthesis of the p24 structural protein of FIV. Examination of the possibility that the TSCD are also involved in suppression of the activity of HIV's tat regulatory protein showed a clear dose-responsive inhibition of HIV's tat-mediated transactivation by M-IBDET and A-IBDAT.