The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin
Abstract
Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.
Article and author information
Author details
Reviewing Editor
- Mercedes Pascual, University of Michigan, United States
Publication history
- Received: May 7, 2014
- Accepted: July 3, 2014
- Accepted Manuscript published: July 8, 2014 (version 1)
- Accepted Manuscript updated: July 9, 2014 (version 2)
- Accepted Manuscript updated: July 11, 2014 (version 3)
- Version of Record published: July 29, 2014 (version 4)
Copyright
© 2014, Thyagarajan & Bloom
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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