Sequence Variability in p6 gag Protein and gag/pol Coevolution in Human Immunodeficiency Type 1 Subtype F Genomes

Polymorphisms occurring at the p6(gag) protein of HIV-1 have been previously found to have an impact on viral fitness and antiretroviral (ARV) resistance, mainly on subtype B genomes. We compared p6(gag) variability in a large group of 165 subtype F gag-pol sequences, with 36 subtype B sequences from the same study source, and identified sites of gag-pol coevolution under ARV selection pressure. Subtype-specific differences in the frequency of point mutations, insertions, and deletions previously associated with ARV resistance were found. Also, in our dataset of subtype F genomes a strong association between mutation P5L in the p1/p6 cleavage region of gag and the nelfinavir (NFV) resistance mutation N88D(PR) was found with no impact on the preference for any of the NFV resistance pathways.