Impact of 5-azacytidine and 5-aza-2''-deoxycytidine on the mutagenesis of HIV-1

5-azacytidine (5-aza-C) and 5-aza-2''-deoxycytidine (5-aza-dC) are related nucleoside analogs that are candidates for the induction of lethal mutagenesis in human immunodeficiency virus type-1 (HIV-1). The aim of lethal mutagenesis is to induce a sufficiently high level of deleterious mutations to extinguish viral replication. In this study, Illumina sequencing was performed in order to compare the patterns of viral mutagenesis resulting from HIV-1 exposure to 5-aza-C or 5-aza-dC. This was accomplished by sequencing amplicons prepared from genomic DNA from U373-MAGI cells infected with HIV-1 in the presence or absence of these compounds. Further, the impact of the natural product resveratrol (an inhibitor of the cellular enzyme ribonucleotide reductase) on HIV-1 mutagenesis was assessed alone or in combination with 5-aza-C or 5-aza-dC.