Prediction of immune pressure on HIV-1 regulatory gene tat by human host through bioinformatics tools

In the early establishment of HIV-1 infection, Tat protein plays an essential role in controlling other genes of HIV-1 (e.g., vif, vpr, vpu, nef, gag, pol and env), for viral pathogenesis, while maintaining its polymorphic nature. It is well documented that polymorphism of HIV-1 genome are created to escape immune pressures (e.g. CD8+, CD4+, B, NK-cells and others) by human host, during the course of infection. Over the time those mutations are incorporated or left in the HIV genome as an escaped flag or signature amino acid, and this scenario could be predictable using contemporary bioinformatics tools. Our sequence analysis from global database (LANL) revealed that Tat protein under positive immune pressure as dn/ds >1.5, even though differential immune pressure exists among the HIV-1 subtype. Average entropy score is 0.31, implying the less variable nature of this protein while amino acid variations are higher in C-terminal. Remarkably, the region encompassing by positions 38 to 51 amino acids are relatively conserved, over the year 2009 to 2017 across HIV-1 subtype. Indeed, subtype-specific SNP or signature amino acids were observed in various position of Tat, dominantly in C-terminal end. Our epitope density plot analysis, highlighted CTLs/CD8+ cells play a major role on Tat sequence variation around the globe. Taken together, our analysis illustrated the dynamic nature of polymorphism within HIV-1 proteins, which could be predictable to see the immune-mediated selective pressure by human host on viral genome.