Immune pressure analysis of protease and reverse transcriptase genes of primary HIV-1 subtype C isolates from South Africa

Abstract

Synonymous (ds) and non-synonymous (dn) substitution rates and their ratios (ds/dn) were analyzed for 33 HIV-1 subtype C protease (PR) and reverse transcriptase (RT) nucleotide sequences each from antiretroviral naïve South African chronically infected individuals. The ds/dn ratios were calculated using the synonymous/non-synonymous analysis programme (SNAP). The ds/dn ratio for PR was found to be 5.3801, while for RT it was 8.6098. The RT had a higher ds/dn ratio when compared with PR, suggesting a greater conservation in the RT gene. Generally, these values point to proteins that have not been subjected to strong immune pressure. Analysis of the evolutionary distance of PR and RT based on synonymous and non-synonymous mutations was done by phylogenetic analysis. The clustering of viruses was different when synonymous and non-synonymous substitutions were considered in both gene regions. Overall, the data indicated that the viruses had not experienced high immune pressure at the time the sequences were obtained. It may also mean that, the PR and the RT of the sequences did not present enough epitopes to elicit antibody responses.

Key words: HIV-1 subtype C, chronic infection, immune pressure, protease gene, reverse transcriptase gene, South Africa.