DNA aptamers selected against the HIV-1 RNase H display in vitro antiviralactivity

The DNA polymerase of the human immunodeficiency virus type 1 reverse trans criptase (HIV-1 RT) is a target widely used to inhibit HIV-1 replication. I n contrast, very few inhibitors of the RNase H activity associated with RT have been described, despite the crucial role played by this activity in vi ral proliferation. DNA ligands with a high affinity for the RNase H domain of HIV-1 RT were isolated by systematic evolution of ligands by an exponent ial enrichment strategy (SELEX), using recombinant RTs with or without the RNase H domain. The selected oligonucleotides (ODNs) were able to inhibit i n vitro the HIV-1 RNase H activity, while no effect was observed on cellula r RNase H. We focused our interest on two G-rich inhibitory oligonucleotide s. Model studies of the secondary structure of these ODNs strongly suggeste d that they were able to form G-quartets. In addition to the inhibition of HIV-1 RNase H observed in a cell free system, these ODNs were able to stron gly diminish the infectivity of HIV-1 in human infected cells. Oligonucleot ides described here may serve as leading compounds for the development of s pecific inhibitors of this key retroviral enzyme activity.