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

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.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Kinchington D,Galpin S,Jaroszewski JW,Ghosh K,Subasinghe C,Cohen JS

doi

10.1016/0166-3542(92)90090-r

subject

Has Abstract

pub_date

1992-01-01 00:00:00

pages

53-62

issue

1

eissn

0166-3542

issn

1872-9096

pii

0166-3542(92)90090-R

journal_volume

17

pub_type

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