Models of RNA virus evolution and their roles in vaccine design

Ojosnegros, Samuel; Beerenwinkel, Niko

Immune responses to HIV infection vary depending on the genetic constellation of the human leukocyte antigen (HLA) locus. Antigen-specific T cell immunity is HLA-restricted and therefore mutations in HIV epitopes that allow escape from host immune responses are HLA allele-specific [119, 120] . Cytotoxic T lymphocyte (CTL) escape mutations have been shown to be stable under vertical transmission of the virus [121] . Thus, CTL escape presents an important driving force in shaping HIV evolutionary patterns. Differential HLArestricted viral evolution has been observed in several HIV-1 genes [122] . From a vaccine design point of view, it is pivotal to characterize CTL escape quantitatively in order to address limitations of immune stimulations and to minimize the risk of viral evolutionary escape. This task involves identification of HLA-specific escape mutations and prediction of mutational escape pathways.