Short partially double-stranded oligodeoxynucleotide induces reverse transcriptase/RNase H-mediated cleavage of HIV RNA and contributes to abrogation of infectivity of virions

AIDS Res Hum Retroviruses. 2006 Dec;22(12):1220-30. doi: 10.1089/aid.2006.22.1220.

Abstract

We describe a novel mechanism of viral RNA eradication by an oligodeoxynucleotide A (ODN A) directly in HIV virions. The ODN A consists of an antisense and a passenger strand, and was designed to target the polyp-urine tract (PPT) of HIV-1, a conserved region of the viral genome. It leads to HIV reverse transcriptase/ribonuclease H (RT/RNase H)-dependent degradation of the RNA in viral particles. Illimaquinone, a specific inhibitor of RNase H, activity of HIV RT/RNase H, prevents RNA cleavage. The effect of the ODN A is sequence-specific and the passenger strand is important, since a lack or alteration of this strand reduces the antiviral activity of the ODN. ODN A has a stronger antiviral effect compared to a control ODN CO, targeted to a site outside of the PPT. The pretreatment with ODN A strongly reduced the infectivity of virions in cell culture in the absence of any DNA carriers or detergents.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Base Sequence
  • Cells, Cultured
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / genetics*
  • HIV-1 / pathogenicity
  • Molecular Sequence Data
  • Oligonucleotides, Antisense / biosynthesis
  • Oligonucleotides, Antisense / pharmacology*
  • RNA Stability / genetics*
  • RNA, Viral / metabolism*
  • Ribonuclease H / metabolism
  • Virion / genetics*
  • Virion / pathogenicity

Substances

  • Antiviral Agents
  • Oligonucleotides, Antisense
  • RNA, Viral
  • HIV Reverse Transcriptase
  • Ribonuclease H