Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift

Overview

Journal Science

Specialty Science

Date 2009 Nov 11

PMID 19900932

Citations 283

Authors

Scott E Hensley

Suman R Das

Adam L Bailey

Loren M Schmidt

Heather D Hickman

Akila Jayaraman

Karthik Viswanathan

Rahul Raman

Ram Sasisekharan

Jack R Bennink

Jonathan W Yewdell

Affiliations

Soon will be listed here.

Abstract

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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