Seasonal influenza viruses are subjected to strong selection as seen by the sequential replacement of existing viral populations on the emergence of new antigenic variants. However, the process of within-host de novo mutant generation and evolutionary selection that underlies these antigenic sweeps is poorly understood. Here, we investigate mutational patterns between evolutionarily closely related human seasonal influenza viruses using host age as a proxy for immune experience. The systematic analysis of >25,000 virus sequences showed that individuals with substantially differing immune histories were frequently (30–62%) infected by viruses with identical amino acid sequences. Viruses from immunologically inexperienced individuals were as likely to possess substitutions with potential phenotypic relevance as highly experienced individuals. Mutations likely to cause antigenic changes were rare among closely related viruses and not associated with extent of host immune experience. These findings suggest that individual immune positive selection plays a limited role in the evolution of seasonal influenza viruses.
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Processed data, including curated sequence alignments, metadata and phylogenetic trees generated, are available on Github: http://github.com/alvinxhan/ageflu.
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We thank the GISAID Initiative and the influenza surveillance and research groups that openly shared the genetic sequence data that made this work possible. A.X.H. was supported by the A*STAR Graduate Scholarship programme from A*STAR to carry out his PhD work via collaboration between Bioinformatics Institute (A*STAR) and NUS Graduate School for Integrative Sciences and Engineering from the National University of Singapore. S.M.S. was supported by the A*STAR HEIDI programme (grant number H1699f0013) and Bioinformatics Institute (A*STAR). C.A.R. was supported by University Research Fellowship from the Royal Society.
The authors declare no competing interests.
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Han, A.X., Maurer-Stroh, S. & Russell, C.A. Individual immune selection pressure has limited impact on seasonal influenza virus evolution. Nat Ecol Evol 3, 302–311 (2019). https://doi.org/10.1038/s41559-018-0741-x
Nature Ecology & Evolution (2019)