Back to Search Start Over

Hemagglutinin receptor binding avidity drives influenza A virus antigenic drift.

Authors :
Hensley SE
Das SR
Bailey AL
Schmidt LM
Hickman HD
Jayaraman A
Viswanathan K
Raman R
Sasisekharan R
Bennink JR
Yewdell JW
Source :
Science (New York, N.Y.) [Science] 2009 Oct 30; Vol. 326 (5953), pp. 734-6.
Publication Year :
2009

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.

Details

Language :
English
ISSN :
1095-9203
Volume :
326
Issue :
5953
Database :
MEDLINE
Journal :
Science (New York, N.Y.)
Publication Type :
Academic Journal
Accession number :
19900932
Full Text :
https://doi.org/10.1126/science.1178258