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  Major antigenic site B of human influenza H3N2 viruses has an evolving local fitness landscape

Wu, N. C., Otwinowski, J., Thompson, A. J., Nycholat, C. M., Nourmohammad, A., & Wilson, I. A. (2020). Major antigenic site B of human influenza H3N2 viruses has an evolving local fitness landscape. Nature Communications, 11(1): 1233. doi:10.1038/s41467-020-15102-5.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-DC22-D Version Permalink: http://hdl.handle.net/21.11116/0000-0005-DE7F-4
Genre: Journal Article

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Wu, N. C., Author
Otwinowski, Jakub1, Author              
Thompson, A. J., Author
Nycholat, C. M., Author
Nourmohammad, Armita2, Author              
Wilson, I. A., Author
Affiliations:
1Max Planck Research Group Biological Physics and Evolutionary Dynamics, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society, ou_2063291              
2Max Planck Research Group Statistical physics of evolving systems, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society, ou_2516692              

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 Abstract: Antigenic drift of influenza virus hemagglutinin (HA) is enabled by facile evolvability. However, HA antigenic site B, which has become immunodominant in recent human H3N2 influenza viruses, is also evolutionarily constrained by its involvement in receptor binding. Here, we employ deep mutational scanning to probe the local fitness landscape of HA antigenic site B in six different human H3N2 strains spanning from 1968 to 2016. We observe that the fitness landscape of HA antigenic site B can be very different between strains. Sequence variants that exhibit high fitness in one strain can be deleterious in another, indicating that the evolutionary constraints of antigenic site B have changed over time. Structural analysis suggests that the local fitness landscape of antigenic site B can be reshaped by natural mutations via modulation of the receptor-binding mode. Overall, these findings elucidate how influenza virus continues to explore new antigenic space despite strong functional constraints.

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Language(s): eng - English
 Dates: 2020-03-06
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.1038/s41467-020-15102-5
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Title: Nature Communications
Source Genre: Journal
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Pages: 10 Volume / Issue: 11 (1) Sequence Number: 1233 Start / End Page: - Identifier: -