
<ArticleTitle>DNA aptamers selected against the HIV-1 <prot>RNase H</prot> display in vitro antiviral activity.</ArticleTitle>
<AbstractText>The DNA polymerase of the human immunodeficiency virus type 1 <prot>reverse transcriptase</prot> (HIV-1 <prot>RT</prot>) is a target widely used to inhibit HIV-1 replication. In contrast, very few inhibitors of the <prot>RNase H</prot> activity associated with <prot>RT</prot> have been described, despite the crucial role played by this activity in viral proliferation. DNA ligands with a high affinity for the <prot>RNase H</prot> domain of HIV-1 <prot>RT</prot> were isolated by systematic evolution of ligands by an exponential enrichment strategy (SELEX), using recombinant <prot>RT</prot>s with or without the <prot>RNase H</prot> domain. The selected oligonucleotides (ODNs) were able to inhibit in vitro the HIV-1 <prot>RNase H</prot> activity, while no effect was observed on cellular <prot>RNase H</prot>. We focused our interest on two G-rich inhibitory oligonucleotides. Model studies of the secondary structure of these ODNs strongly suggested that they were able to form G-quartets. In addition to the inhibition of HIV-1 <prot>RNase H</prot> observed in a cell free system, these ODNs were able to strongly diminish the infectivity of HIV-1 in human infected cells. Oligonucleotides described here may serve as leading compounds for the development of specific inhibitors of this key retroviral enzyme activity.</AbstractText>
