Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift
Author(s)Hensley, Scott E.; Das, Suman R.; Bailey, Adam L.; Schmidt, Loren M.; Hickman, Heather D.; Bennink, Jack R.; Yewdell, Jonathan W.; Jayaraman, Akila; Viswanathan, Karthik; Raman, Rahul; Sasisekharan, Ram; ... Show more Show less
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Rapid antigenic evolution in the influenza A virus hemagglutinin precludes effective vaccination with existing vaccines. To understand this phenomenon, we passaged virus in mice immunized with influenza vaccine. Neutralizing antibodies selected mutants with single–amino acid hemagglutinin substitutions that increased virus binding to cell surface glycan receptors. Passaging these high-avidity binding mutants in naïve mice, but not immune mice, selected for additional hemagglutinin substitutions that decreased cellular receptor binding avidity. Analyzing a panel of monoclonal antibody hemagglutinin escape mutants revealed a positive correlation between receptor binding avidity and escape from polyclonal antibodies. We propose that in response to variation in neutralizing antibody pressure between individuals, influenza A virus evolves by adjusting receptor binding avidity via amino acid substitutions throughout the hemagglutinin globular domain, many of which simultaneously alter antigenicity.
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DepartmentHarvard University--MIT Division of Health Sciences and Technology; Koch Institute for Integrative Cancer Research at MIT
American Association for the Advancement of Science
Hensley, S. E. et al. “Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift.” Science 326 (2009): 734-736. Web. 16 Nov. 2011. © 2009 American Association for the Advancement of Science
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