A comparison of gag, pol and rev antisense oligodeoxynucleotides as inhibitors of HIV-1

Antiviral Res. 1992 Jan;17(1):53-62. doi: 10.1016/0166-3542(92)90090-r.

Abstract

Sequences from the gag, pol and rev regions of the RF strain of HIV-1 (HIV-1RF) were chosen as targets for antisense phosphorothioate oligodeoxynucleotides (S-oligos). These sequences were the p18/p24 junction in gag, the active site of HIV protease in pol; a sequence from the first exon of the rev gene and S-oligodeoxycytidylic acid controls. Compounds were tested against HIV-1 in both acutely and chronically infected cells. The results show that these phosphorothioate analogues tested in acutely infected cells were active in the 0.1-2 microM range, were dependent on chain length but had no sequence specificity. To study the mechanism of action, the time of addition of S-oligos to acutely infected cells was delayed for up to 48 h post-infection. It was found that antiviral activity was lost when compounds were added to the cultures later than 10 h post-infection. With chronically infected cells only the antisense rev sequence showed activity at 30 microM and neither of the gag or pol antisense sequences has a significant effect on HIV replication at 50 microM. These results are consistent with previous in vitro studies which demonstrate that antisense S-oligodeoxynucleotides have several modes of action.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Base Sequence / drug effects
  • Cell Line
  • Genes, gag / drug effects*
  • Genes, pol / drug effects*
  • Genes, rev / drug effects*
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Lymphocytes
  • Molecular Sequence Data
  • Oligonucleotides, Antisense / pharmacology*
  • Thionucleotides / pharmacology

Substances

  • Antiviral Agents
  • Oligonucleotides, Antisense
  • Thionucleotides