Models of RNA virus evolution and their roles in vaccine design

Ojosnegros, Samuel; Beerenwinkel, Niko

HIV polymorphisms associated with CTL escape leave HLA-specific footprints at the population level and hence detection of escape mutations is based on the comparative method. However, there are at least three confounding factors in this approach. First, viral sequences obtained from different hosts cannot be regarded as independent observations of the same stochastic process. Rather, these sequences share a common evolutionary history. Second, structural and functional limitations, such as the biophysics of threedimensional protein structures, impose constraints on codon covariation and give rise to linkage disequilibrium (LD) in the HIV genome. Third, the host's HLA genes are also in LD because of their close physical distance on human chromosome 6.