Short partially double-stranded oligodeoxynucleotide induces reverse transcriptase/RNase H-mediated cleavage of HIV RNA and contributes to abrogation of infectivity of virions.
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.
Matskevich
Alexey A
AA
Institute of Medical Virology, University of Zurich, CH-8006 Zurich, Switzerland.
Ziogas
Algirdas
A
Heinrich
Jochen
J
Quast
Sandra A
SA
Moelling
Karin
K
D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D002478:Cells, Cultured; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000096:biosynthesis / Q000494:pharmacology*; D020871:RNA Stability / Q000235:genetics*; D012367:RNA, Viral / Q000378:metabolism*; D016914:Ribonuclease H / Q000378:metabolism; D014771:Virion / Q000235:genetics* / Q000472:pathogenicity
D000998:Antiviral Agents; D016376:Oligonucleotides, Antisense; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016914:Ribonuclease H