Short communication: Nucleotide variation and positively selected sites in HIV type 1 reverse transcriptase among heterosexual transmission pairs

Mutations in the env gene of HIV-1 have been the primary focus in most epidemiologically related cohort studies of virus evolution and very limited studies have focused on the reverse transcriptase (RT) region, the primary target of antiretroviral therapy (ART). Hence, we measured the selection pressure and searched for the positively selected sites in the RT sequences amplified from HIV-1-infected heterosexual transmission pairs. Married couples (n=10) who were ART naive were included in this study. Phylogenetic analysis, the measurement of synonymous and nonsynonymous ratio (dN/dS) and the interpatient nucleotide variation, was done. Phylogenetic analysis demonstrated distinct subclusters of the RT sequences from heterosexual transmission pairs and the median (IQR) nucleotide variation between the epidemiologically related transmission pairs was significantly (p<0.001) lower [0.01% (0.01-0.02%)] compared to the epidemiologically unrelated transmission pairs [0.04% (0.03-0.04%)]. The ratio of dN/dS was <1 and codons 135, 162, 166, 207, and 211 were positively selected in >50% of the donor and recipient RT sequences. Purifying selection pressure and low nucleotide variation in the RT sequences between epidemiologically related transmission pairs highlight its essential role in HIV-1 replication. The effect of the RT positively selected mutations that persist over time following transmission between individuals needs to be studied to determine the fitness cost of the mutations in vivo, which may possibly represent good targets for inclusion in HIV-1 vaccines.