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Inferring polygenic selection for HIV escape from T cell responses

ORAL

Abstract

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.

Publication: [1] Allen, T. M. et al. "Selective escape from CD8+ T-cell responses represents a major driving force of human immunodeficiency virus type 1 (HIV-1) sequence diversity and reveals constraints on HIV-1 evolution. " J. Virol. 79 (2005): 13239–13249.<br>[2] Sohail, Muhammad Saqib, et al. "MPL resolves genetic linkage in fitness inference from complex evolutionary histories." Nature <br>Biotechnology 39.4 (2021): 472-479.

Presenters

  • Yirui Gao

    univeristy of california, riverside

Authors

  • Yirui Gao

    univeristy of california, riverside

  • John P Barton

    University of California, Riverside