Hensley, S. E., Das, S. R., Bailey, A. L., Schmidt, L. M., Hickman, H. D., Jayaraman, A., Viswanathan, K., Raman, R., Sasisekharan, R., Bennink, J. R., Yewdell, J. W.
Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift
Science. 2009 Oct 30; 326(5953): 734-6.
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 naive 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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