tetano
Editor, Senior Moderator
Science 22 November 2013:
Vol. 342 no. 6161 pp. 976-979
DOI: 10.1126/science.1244730
Report
Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution
Bj?rn F. Koel1,
David F. Burke2,3,
Theo M. Bestebroer1,
Stefan van der Vliet1,
Gerben C. M. Zondag4,5,
Gaby Vervaet1,
Eugene Skepner2,3,
Nicola S. Lewis2,3,
Monique I. J. Spronken1,
Colin A. Russell3,6,
Mikhail Y. Eropkin7,
Aeron C. Hurt8,
Ian G. Barr8,
Jan C. de Jong1,
Guus F. Rimmelzwaan1,
Albert D. M. E. Osterhaus1,
Ron A. M. Fouchier1,*,
Derek J. Smith1,2,3,9,*
+ Author Affiliations
1Department of Viroscience, Erasmus MC, 3015GE Rotterdam, Netherlands.
2Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.
3WHO Collaborating Centre for Modeling Evolution and Control of Emerging Infectious Diseases, University of Cambridge, Cambridge CB2 3EJ, UK.
4BaseClear B.V., 2333CC Leiden, Netherlands.
5Luris, Leiden University, 2333AA Leiden, Netherlands.
6Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
7Research Institute of Influenza, 197376 St. Petersburg, Russia.
8WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, Melbourne, Victoria 3051, Australia.
9Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA.
↵*Corresponding author. E-mail: dsmith@zoo.cam.ac.uk (D.J.S.); r.fouchier@erasmusmc.nl (R.A.M.F.)
Abstract
Editor's Summary
The molecular basis of antigenic drift was determined for the hemagglutinin (HA) of human influenza A/H3N2 virus. From 1968 to 2003, antigenic change was caused mainly by single amino acid substitutions, which occurred at only seven positions in HA immediately adjacent to the receptor binding site. Most of these substitutions were involved in antigenic change more than once. Equivalent positions were responsible for the recent antigenic changes of influenza B and A/H1N1 viruses. Substitution of a single amino acid at one of these positions substantially changed the virus-specific antibody response in infected ferrets. These findings have potentially far-reaching consequences for understanding the evolutionary mechanisms that govern influenza viruses.
http://www.sciencemag.org/content/342/6161/976.abstract
Vol. 342 no. 6161 pp. 976-979
DOI: 10.1126/science.1244730
Report
Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution
Bj?rn F. Koel1,
David F. Burke2,3,
Theo M. Bestebroer1,
Stefan van der Vliet1,
Gerben C. M. Zondag4,5,
Gaby Vervaet1,
Eugene Skepner2,3,
Nicola S. Lewis2,3,
Monique I. J. Spronken1,
Colin A. Russell3,6,
Mikhail Y. Eropkin7,
Aeron C. Hurt8,
Ian G. Barr8,
Jan C. de Jong1,
Guus F. Rimmelzwaan1,
Albert D. M. E. Osterhaus1,
Ron A. M. Fouchier1,*,
Derek J. Smith1,2,3,9,*
+ Author Affiliations
1Department of Viroscience, Erasmus MC, 3015GE Rotterdam, Netherlands.
2Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.
3WHO Collaborating Centre for Modeling Evolution and Control of Emerging Infectious Diseases, University of Cambridge, Cambridge CB2 3EJ, UK.
4BaseClear B.V., 2333CC Leiden, Netherlands.
5Luris, Leiden University, 2333AA Leiden, Netherlands.
6Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
7Research Institute of Influenza, 197376 St. Petersburg, Russia.
8WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, Melbourne, Victoria 3051, Australia.
9Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA.
↵*Corresponding author. E-mail: dsmith@zoo.cam.ac.uk (D.J.S.); r.fouchier@erasmusmc.nl (R.A.M.F.)
Abstract
Editor's Summary
The molecular basis of antigenic drift was determined for the hemagglutinin (HA) of human influenza A/H3N2 virus. From 1968 to 2003, antigenic change was caused mainly by single amino acid substitutions, which occurred at only seven positions in HA immediately adjacent to the receptor binding site. Most of these substitutions were involved in antigenic change more than once. Equivalent positions were responsible for the recent antigenic changes of influenza B and A/H1N1 viruses. Substitution of a single amino acid at one of these positions substantially changed the virus-specific antibody response in infected ferrets. These findings have potentially far-reaching consequences for understanding the evolutionary mechanisms that govern influenza viruses.
http://www.sciencemag.org/content/342/6161/976.abstract