On the nucleotide composition and structure of retroviral RNA genomes

Retroviral RNA genomes display a rich variety in their nucleotide composition. For instance, the single-stranded RNA genome of human T cell leukemia virus (HTLV-1) is C-rich and G-poor and that of the human immunodeficiency virus (HIV-1) is A-rich and C-poor. Animal retroviruses add further variation to this unexplained, but many times remarkable virus-specific property. We previously described that the nucleotide bias is even more extreme in the unpaired regions of the structured HIV-1 RNA genome, which has been probed by SHAPE technology. We now document that the same trend is apparent for the MFold-predicted RNA structure of HIV-1 RNA and subsequently investigated the predicted structures of the RNA genomes of other retroviruses. We conclude that all virus-specific signatures are enhanced for the unpaired nucleotides in the RNA genome. Consequently, the differences in nucleotide count between the diverse human and animal retroviruses are further exposed in the single stranded genome regions. We used a skew analysis to visualize these striking differences in nucleotide usage. Evolutionary events responsible for these nucleotide signatures will be discussed.