Inhibition of murine leukemia viruses by nuclease-resistant alpha-oligonucleotides

We studied the antiviral activity of nuclease-resistant alpha-anomeric oligonucleotides. An alpha-oligonucleotide (20-mer) targeted to the primer binding site (PBS) of murine retroviruses inhibited viral spreading. The inhibition only occurred when the cells had been electropermeabilized in the presence of the oligonucleotide. The PBS sequence is involved in reverse transcription and in translation. The data suggest that the oligonucleotide could perturb reverse transcription activity. Thus, either the oligonucleotide induced a decrease in initiation or it inhibited the extension of the minus or plus strands DNA during reverse transcription. These results show that reverse transcription may be an interesting target for antisense oligonucleotides.