a, Most hypermutated proviruses show both GG→AG and GA→AA patterns of hypermutation. Analysis based on hypermutated full-genome sequences in the database (n = 100). Sequences were analysed for GG→AG and GA→AA patterns using all available sequences for each clone and the Los Alamos Hypermut algorithm17. b, Hypermutation discrimination using two probes in the RRE of the env gene. The intact probe hybridizes with a region containing two adjacent APOBEC3G consensus sites (red underline) in intact proviruses. It is labelled with a fluorophore (VIC) and a quencher (Q). Also present in the reaction is a hypermutated probe that lacks the fluorophore and does not bind (arrow) to intact proviral sequences owing to G→A mutations at both APOBEC3G consensus sites. Dashed boxes indicate the nucleotide positions of sequence differences between the intact and hypermutated probes. The hypermutated probe preferentially binds to the same region in hypermutated proviruses. It lacks a fluorophore and prevents binding of the fluorophore-labelled intact probe (arrow). Therefore, no fluorescent signal is generated for 95% of hypermutated proviruses (Fig. 2f).