Patterns of nucleotide substitutions and implications for the immunological diversity of human immunodeficiency virus

Human immunodeficiency virus (HIV) exhibits immunological hypervariability, which has been an obstacle to successful production of effective anti-HIV vaccines. In this study, we estimated patterns of nucleotide and amino acid substitutions in the env gene of HIVs, with the aim of finding characteristics of the mechanism which generates the immunological diversity of the env protein of HIVs. We found that nucleotide changes between A and G are predominant compared to those between other nucleotides. Since this feature is consistent with the pattern of nucleotide substitutions of other retroviral genes but is quite different from those of most eukaryotic genes, a high rate of nucleotide substitution between A and G appears to be specific for retroviruses including HIVs. We discuss the biological relationship between this biased substitution and the mechanism generating hypervariability of epitopes on the env protein of HIVs.