Immune Relaxation Hypothesis • Evolutionary rates slow due to disrupting immune function • In relation to our claims, the virus infects specific CD4+ T cell count. • The immune system is the positive selecting agent in C2-V5 region of env. • In relation to Aids, the immune effectors and the virus can alter the course of evolution. • Lower dS/dN ratios were observed in a single patient • Even out to equilibrium • CD4+ T Cells disrupted by infection respond to epitopes coded by env and in driving env sequence evolution.
Divergence • Non-synonymous divergence stabilizes • Seems to coincide with disease progression • Synonymous divergence does not seem to stabilize • Phylogenetic methods can’t be used per say in this paper • No recombination is generally assumed • And studies show that recombination rate in HIV populations in vivo is high
Ratios • dN/dS ratios • > 1 indicates widespread adaptive evolution • Most common among data sets, indicative of positive selection • < 1 some sites are selectively constrained • For our studies, < 1 indicated AIDs and > 1 indicated no AIDs
CD4+ T Cells • In direct correlation with distinguishing AIDs • Subjects < 300 AIDs • Related it back to < 200 from previous graphs and tables. • “Feedback loop” in play. Virus impairs HIV specific responses
Findings • 11/15 AIDs • CD4 T Cell Count • dN/dS ratio • New ?’s