It has been demonstrated in in vitro protein evolution experiments that the most viable of the chimaeric proteins that are expressed from recombinant genes tend to have lower degrees of predicted folding disruption relative to Calindol hydrochloride wild-type proteins than do randomly generated chimaeras. Importantly, similar observations have been made when extending this approach to the analysis of chimaeric virus proteins that both occur naturally and emerge during evolution experiments. An obvious explanation of these tendencies is that recombinants expressing chimaeric proteins in which certain necessary intra-protein amino acid interactions are maintained will have a higher likelihood of replicating and Bis-Imidazole phenol IDH1 inhibitor surviving, whereas those that don��t will be purged by selective processes. Besides potentially disrupting intra-protein amino acid interactions, it is similarly possible that whenever biologically functional nucleic acid secondary structures are present within virus genomes, recombination could disrupt nucleotide-nucleotide interactions within these. When in their single-stranded RNA configuration, HIV genomes have a high degree of secondary structure, much of which is potentially biologically functional. It is expected that recombinants in which biologically functional secondary structures are undisrupted should be more viable than those in which they are disrupted and, therefore, that natural recombinant genomes might display lower degrees of predicted secondary structural disruption than is expected if the maintenance of secondary structures had no evolutionary significance. While evidence of this has been observed amongst recombinant virus genomes arising during in vitro recombination experiments, it remains to be discovered whether such selection might have a detectable impact on patterns of virus recombination that arise under natural conditions. Here we test whether the distinctive recombination patterns evident within naturally occurring HIV genomes display signs of selection disfavouring the survival of recombinants with either recombinationally disrupted intra-protein interactions or recombinationally disrupted RNA secondary structures.