TY - JOUR T1 - Estimating the Fitness Cost of Escape from HLA Presentation in HIV-1 Protease and Reverse Transcriptase A1 - Mostowy, Rafal A1 - Kouyos, Roger D. A1 - Hoof, Ilka A1 - Hinkley, Trevor A1 - Haddad, Mojgan A1 - Whitcomb, Jeannette M. A1 - Petropoulos, Christos J. A1 - Keşmir, Can A1 - Bonhoeffer, Sebastian Y1 - 2012/05/24 N2 - Author Summary Our immune system can recognize and kill virus-infected cells by distinguishing between self and virus-derived protein fragments, called peptides, displayed on the surface of each cell. One requirement for a successful recognition is that those peptides bind to the human leukocyte antigen (HLA) class I molecules, which present them to the immune system. As a counter-strategy, human immunodeficiency virus type 1 (HIV-1) can acquire mutations that prevent this binding, thereby helping the virus to escape the surveillance of T-lymphocytes. It is likely that the virus pays a replicative cost for such escape mutations, but the magnitude of this cost has remained elusive. Here, we quantified this fitness cost in HIV-1 protease and reverse transcriptase by combining two computational systems biology approaches: one for prediction of in vitro replicative fitness, and one for the prediction of the efficiency of peptide binding to HLA. We found that in viral proteins targeted by HLA-A molecules, mutations which disrupt binding to those molecules carry a lower replicative fitness than mutations which do not have such an effect. We argue that these results are consistent with the hypothesis that our immune systems might have evolved to target genetic regions of RNA viruses which are costly for the pathogen to alter. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 8 IS - 5 UR - https://doi.org/10.1371/journal.pcbi.1002525 SP - e1002525 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1002525 ER -