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Hemagglutinin receptor binding avidity drives influenza A virus antigenic drift.
- 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.
- Subjects :
- Animals
Antibodies, Neutralizing immunology
Antibodies, Viral immunology
Antigenic Variation genetics
Cell Line
Hemagglutinin Glycoproteins, Influenza Virus genetics
Hemagglutinin Glycoproteins, Influenza Virus immunology
Influenza A Virus, H1N1 Subtype genetics
Influenza Vaccines immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Models, Immunological
Mutation
Serial Passage
Antigenic Variation immunology
Hemagglutinin Glycoproteins, Influenza Virus metabolism
Influenza A Virus, H1N1 Subtype immunology
Receptors, Virus metabolism
Subjects
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