The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin

eLife

Jesse D Bloom¹  Bargavi Thyagarajan² 

[1] Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, United States;Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States;

关键词: influenza;    hemagglutinin;    phylogenetic;    evolvability;    antigenic evolution;    deep mutational scanning;   

DOI  :  10.7554/eLife.03300

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown