ANTIVIRAL ACTION OF OLIGODEOXYGUANYLIC ACIDS AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Deoxyguanylic acids, but not other deoxynucleotides, as short as 3- to 4-mer, were effective in preventing HIV-1-induced cytopathicity, In a ddition, they prevented giant cell formation of infected Sup-T1 cells, and p24 production in HIV-1 infected H9 cells, Phosphorylation at eit her the 5'- or 3'-end enhanced these activities, Furthermore, 5'-phosp horylated phosphorothioate tetradeoxyguanylic acid was effective in re ducing HIV production in chronically infected cells (H9/IIIB). The sea rch for the target steps of this compound revealed that it inhibits at least 3 steps in the life cycle of HIV: interaction with CD4 (measure d by inhibitory effect on the syncytia formation between Sup-T1 and H9 /IIIB cells), reverse transcriptase, and step(s) after integration, Th ese results suggest that phosphorylated phosphorothioate tetradeoxygua nylic acid may be a novel candidate for a therapeutic agent of AIDS.