The ongoing evolutionary battle between the immune system and viruses : MHC molecules verus HIV

Abstract

We investigated the evolutionary battle between hosts and pathogens by focusing on the evolution of MHC molecules and HIV-1. We used computational methods to get more insight on the selection pressure they impose on each other. First we studied the footprints of an SIV like pathogen on Patr (chimpanzee MHC) molecules by comparing their functionality with that of contemporary HLA molecules. Next we switched to HIV-1 and investigated whether the HIV-1 genome has adapted to the human population since the relatively short time of infection in humans. We showed that the number of epitopes predicted to bind to protective HLA molecules decreased after 20 years of HIV-1 infection, suggesting that the adaption of HIV-1 is driven by protective HLA molecules. To understand the impact of HLA molecules on the control of HIV-1 infection, we focused on both the evolution of HLA molecules and the escape dynamics of HIV-1. For the former, we zoomed into the peptide binding groove and investigated effect of single substitutions on the function of the molecule. For the latter we used a mathematical model and showed that the escape rate of HIV-1 slows down when the breadth of the CTL response increases. Finally, to understand how an intervention, like a therapeutic vaccination, could change the interplay with the virus and its host, we analyzed the variation in HIV-1 sequences before and after an therapeutic intervention and found that, at least in the trial where we had data available, the effect of a therapeutic vaccine on HIV-1 evolution is negligible