Giuseppe
Emeritus
Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift (Science, abstract, edited)
Science 30 October 2009: Vol. 326. no. 5953, pp. 734 - 736
DOI: 10.1126/science.1178258
Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift
Scott E. Hensley,1 Suman R. Das,1 Adam L. Bailey,1 Loren M. Schmidt,1 Heather D. Hickman,1 Akila Jayaraman,2 Karthik Viswanathan,2 Rahul Raman,2 Ram Sasisekharan,2 Jack R. Bennink,1 Jonathan W. Yewdell1,*
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 na?ve 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.
1 Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
2 Harvard-MIT Division of Health Sciences and Technology, Koch Institute for Integrative Cancer Research and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
* To whom correspondence should be addressed. E-mail: jyewdell@mail.nih.gov
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<cite cite="http://www.sciencemag.org/cgi/content/abstract/326/5953/734">Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift -- Hensley et al. 326 (5953): 734 -- Science</cite>DOI: 10.1126/science.1178258
Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift
Scott E. Hensley,1 Suman R. Das,1 Adam L. Bailey,1 Loren M. Schmidt,1 Heather D. Hickman,1 Akila Jayaraman,2 Karthik Viswanathan,2 Rahul Raman,2 Ram Sasisekharan,2 Jack R. Bennink,1 Jonathan W. Yewdell1,*
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 na?ve 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.
1 Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
2 Harvard-MIT Division of Health Sciences and Technology, Koch Institute for Integrative Cancer Research and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
* To whom correspondence should be addressed. E-mail: jyewdell@mail.nih.gov
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