Unknown

Dataset Information

0

Hemagglutinin receptor binding avidity drives influenza A virus antigenic drift.


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.

SUBMITTER: Hensley SE 

PROVIDER: S-EPMC2784927 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications


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  ...[more]

Similar Datasets

| S-EPMC3754131 | biostudies-literature
| S-EPMC3747226 | biostudies-literature
| S-EPMC3479480 | biostudies-literature
| S-EPMC5668287 | biostudies-literature
| S-EPMC7527056 | biostudies-literature
| S-EPMC7077184 | biostudies-literature
| S-EPMC3251064 | biostudies-literature
| S-EPMC3165837 | biostudies-literature
| S-EPMC6116000 | biostudies-literature
| S-EPMC5008105 | biostudies-literature