Inferring polygenic selection for HIV escape from T cell responses*

Polygenic selection refers to natural selection that acts through multiple mutations. As one example, HIV mutation to escape from human T cell responses can be thought of as polygenic adaptation in the sense that any nonsynonymous mutations within the epitope can allow the virus to escape immune recognition and hence enhance its fitness [1]. Here we build a model describing this polygenic immune selection. We also extend the Marginal Path Likelihood [2] method to this model to infer selection from evolutionary histories. Simulations show the validity of our method. Applying our approach to within-host HIV evolutionary histories, we observe strong selection to escape from T cell responses across the HIV genome.