Glycan Clock Forecasts Human Influenza A Virus Hemagglutinin Evolution

Adaptive immunity to influenza A virus is limited by frequent mutations in the immunodominant head of hemagglutinin (HA). Over the last century, the upward trend in HA-head glycosylation indicates glycan addition can increase fitness, but its role in viral evolution remains unclear. Here, we report...

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Bibliographic Details
Published inbioRxiv
Main Authors Altman, Meghan O, Angel, Matthew, Ivan Ko k, Gibbs, James S, N dia S Trov o, Zost, Seth J, Hensley, Scott E, Nelson, Martha I, Yewdell, Jonathan W
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 25.08.2017
Subjects
Adaptive immunity
Evolution
Glycosylation
Hemagglutinins
Influenza
Influenza A
Pandemics
Polysaccharides
Reproductive fitness
Strains (organisms)
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Summary:Adaptive immunity to influenza A virus is limited by frequent mutations in the immunodominant head of hemagglutinin (HA). Over the last century, the upward trend in HA-head glycosylation indicates glycan addition can increase fitness, but its role in viral evolution remains unclear. Here, we report glycan evolution follows a clock-like rhythm, pacing the timeline, trajectory, and replacement of HA. Following pandemic introduction, glycans are added to HA at 4- to 6-year intervals, until a functional glycan limit is reached, after which, at 9- to 12-year intervals, glycans are either swapped between different sites, or the HA is replaced by a novel pandemic virus. Using this, we predicted the appearance of the newest glycan on pH1N1 HA. Phylogeographic reconstruction suggests these highly fit strains originated in the Middle East, before rapidly replacing all strains globally. Going forward, we can use this simple algorithm to forecast future glycan evolution and identify seasons with higher pandemic potential.
DOI:10.1101/163345