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The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin.

Thyagarajan B, Bloom JD - Elife (2014)

Bottom Line: We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.

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 ≈10(4) 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.

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Related in: MedlinePlus

A phylogenetic tree of the same sequences shown in Figure 8, this time inferred using the substitution model of Kosiol et al. (2007).This tree is extremely similar to that in Figure 8, indicating the inferred topology is robust to the exact choice of codon-substitution model. This plot is the file CodonPhyML_Tree_H1_HumanSwine_KOSI07/annotated_tree.pdf described at http://jbloom.github.io/phyloExpCM/example_2014Analysis_Influenza_H1_HA.html.DOI:http://dx.doi.org/10.7554/eLife.03300.017
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fig8s1: A phylogenetic tree of the same sequences shown in Figure 8, this time inferred using the substitution model of Kosiol et al. (2007).This tree is extremely similar to that in Figure 8, indicating the inferred topology is robust to the exact choice of codon-substitution model. This plot is the file CodonPhyML_Tree_H1_HumanSwine_KOSI07/annotated_tree.pdf described at http://jbloom.github.io/phyloExpCM/example_2014Analysis_Influenza_H1_HA.html.DOI:http://dx.doi.org/10.7554/eLife.03300.017

Mentions: The WSN virus used in the experiments here is a lab-adapted version of the A/Wilson Smith/1933 strain. Human H1N1 that circulated from 1918 until 1957 is shown in blue. Human seasonal H1N1 that reappeared in 1977 is shown in purple. Swine H1N1 is shown in red. The 2009 pandemic H1N1 is shown in green. This tree was constructed using codonPhyML (Gil et al., 2013) with the substitution model of Goldman and Yang (1994). This plot is the file CodonPhyML_Tree_H1_HumanSwine_GY94/annotated_tree.pdf described at http://jbloom.github.io/phyloExpCM/example_2014Analysis_Influenza_H1_HA.html. Figure 8—figure supplement 1 shows a tree estimated for the same sequences using the substitution model of Kosiol et al. (2007).


The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin.

Thyagarajan B, Bloom JD - Elife (2014)

A phylogenetic tree of the same sequences shown in Figure 8, this time inferred using the substitution model of Kosiol et al. (2007).This tree is extremely similar to that in Figure 8, indicating the inferred topology is robust to the exact choice of codon-substitution model. This plot is the file CodonPhyML_Tree_H1_HumanSwine_KOSI07/annotated_tree.pdf described at http://jbloom.github.io/phyloExpCM/example_2014Analysis_Influenza_H1_HA.html.DOI:http://dx.doi.org/10.7554/eLife.03300.017
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109307&req=5

fig8s1: A phylogenetic tree of the same sequences shown in Figure 8, this time inferred using the substitution model of Kosiol et al. (2007).This tree is extremely similar to that in Figure 8, indicating the inferred topology is robust to the exact choice of codon-substitution model. This plot is the file CodonPhyML_Tree_H1_HumanSwine_KOSI07/annotated_tree.pdf described at http://jbloom.github.io/phyloExpCM/example_2014Analysis_Influenza_H1_HA.html.DOI:http://dx.doi.org/10.7554/eLife.03300.017
Mentions: The WSN virus used in the experiments here is a lab-adapted version of the A/Wilson Smith/1933 strain. Human H1N1 that circulated from 1918 until 1957 is shown in blue. Human seasonal H1N1 that reappeared in 1977 is shown in purple. Swine H1N1 is shown in red. The 2009 pandemic H1N1 is shown in green. This tree was constructed using codonPhyML (Gil et al., 2013) with the substitution model of Goldman and Yang (1994). This plot is the file CodonPhyML_Tree_H1_HumanSwine_GY94/annotated_tree.pdf described at http://jbloom.github.io/phyloExpCM/example_2014Analysis_Influenza_H1_HA.html. Figure 8—figure supplement 1 shows a tree estimated for the same sequences using the substitution model of Kosiol et al. (2007).

Bottom Line: We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.

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 ≈10(4) 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.

Show MeSH
Related in: MedlinePlus