A comparison of gag, pol and rev antisense oligodeoxynucleotides as inhibitors of HIV-1.
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.
Kinchington
D
D
Department of Virology, Medical College of St. Bartholomew's Hospital, London, U.K.
Galpin
S
S
Jaroszewski
J W
JW
Ghosh
K
K
Subasinghe
C
C
Cohen
J S
JS
D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence / Q000187:drug effects; D002460:Cell Line; D015750:Genes, gag / Q000187:drug effects*; D015751:Genes, pol / Q000187:drug effects*; D015757:Genes, rev / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008214:Lymphocytes; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology
D000998:Antiviral Agents; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides