Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Originally published in Science Express on 24 June 2004
Science 16 July 2004:
Vol. 305. no. 5682, pp. 371 - 376
DOI: 10.1126/science.1097211
Prev | Table of Contents | Next

Research Articles

Mapping the Antigenic and Genetic Evolution of Influenza Virus

Derek J. Smith,1,2*{dagger} Alan S. Lapedes,3* Jan C. de Jong,2 Theo M. Bestebroer,2 Guus F. Rimmelzwaan,2 Albert D. M. E. Osterhaus,2 Ron A. M. Fouchier2*

The antigenic evolution of influenza A (H3N2) virus was quantified and visualized from its introduction into humans in 1968 to 2003. Although there was remarkable correspondence between antigenic and genetic evolution, significant differences were observed: Antigenic evolution was more punctuated than genetic evolution, and genetic change sometimes had a disproportionately large antigenic effect. The method readily allows monitoring of antigenic differences among vaccine and circulating strains and thus estimation of the effects of vaccination. Further, this approach offers a route to predicting the relative success of emerging strains, which could be achieved by quantifying the combined effects of population level immune escape and viral fitness on strain evolution.

1 Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
2 National Influenza Center and Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015GE Rotterdam, Netherlands.
3 Theoretical Division, T-13, MS B213, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: dsmith{at}zoo.cam.ac.uk

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Incorporating demographic stochasticity into multi-strain epidemic models: application to influenza A.
P. Minayev and N. Ferguson (2009)
J R Soc Interface 6, 989-996
   Abstract »    Full Text »    PDF »
Reemergence of Enterovirus 71 in 2008 in Taiwan: Dynamics of Genetic and Antigenic Evolution from 1998 to 2008.
S.-W. Huang, Y.-W. Hsu, D. J. Smith, D. Kiang, H.-P. Tsai, K.-H. Lin, S.-M. Wang, C.-C. Liu, I.-J. Su, and J.-R. Wang (2009)
J. Clin. Microbiol. 47, 3653-3662
   Abstract »    Full Text »    PDF »
Quantifying the Impact of Immune Escape on Transmission Dynamics of Influenza.
A. W. Park, J. M. Daly, N. S. Lewis, D. J. Smith, J. L. N. Wood, and B. T. Grenfell (2009)
Science 326, 726-728
   Abstract »    Full Text »    PDF »
Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift.
S. E. Hensley, S. R. Das, A. L. Bailey, L. M. Schmidt, H. D. Hickman, A. Jayaraman, K. Viswanathan, R. Raman, R. Sasisekharan, J. R. Bennink, et al. (2009)
Science 326, 734-736
   Abstract »    Full Text »    PDF »
Using a mutual information-based site transition network to map the genetic evolution of influenza A/H3N2 virus.
Z. Xia, G. Jin, J. Zhu, and R. Zhou (2009)
Bioinformatics 25, 2309-2317
   Abstract »    Full Text »    PDF »
The epitope regions of H1-subtype influenza A, with application to vaccine efficacy.
M. W. Deem and K. Pan (2009)
Protein Eng. Des. Sel. 22, 543-546
   Abstract »    Full Text »    PDF »
Antigenic and Genetic Characteristics of Swine-Origin 2009 A(H1N1) Influenza Viruses Circulating in Humans.
R. J. Garten, C. T. Davis, C. A. Russell, B. Shu, S. Lindstrom, A. Balish, W. M. Sessions, X. Xu, E. Skepner, V. Deyde, et al. (2009)
Science 325, 197-201
   Abstract »    Full Text »    PDF »
ATIVS: analytical tool for influenza virus surveillance.
Y.-C. Liao, C.-Y. Ko, M.-H. Tsai, M.-S. Lee, and C. A. Hsiung (2009)
Nucleic Acids Res. 37, W643-W646
   Abstract »    Full Text »    PDF »
Improving the realism of deterministic multi-strain models: implications for modelling influenza A.
P. Minayev and N. Ferguson (2009)
J R Soc Interface 6, 509-518
   Abstract »    Full Text »    PDF »
Herd Immunity to GII.4 Noroviruses Is Supported by Outbreak Patient Sera.
J. L. Cannon, L. C. Lindesmith, E. F. Donaldson, L. Saxe, R. S. Baric, and J. Vinje (2009)
J. Virol. 83, 5363-5374
   Abstract »    Full Text »    PDF »
Differential neutralization efficiency of hemagglutinin epitopes, antibody interference, and the design of influenza vaccines.
W. Ndifon, N. S. Wingreen, and S. A. Levin (2009)
PNAS 106, 8701-8706
   Abstract »    Full Text »    PDF »
Control of equine influenza: scenario testing using a realistic metapopulation model of spread.
M. Baguelin, J.R. Newton, N. Demiris, J. Daly, J.A. Mumford, and J.L.N. Wood (2009)
J R Soc Interface
   Abstract »    Full Text »    PDF »
Influenza sequence and epitope database.
S. Yang, J.-Y. Lee, J. S. Lee, W. P. Mitchell, H.-B. Oh, C. Kang, and K. H. Kim (2009)
Nucleic Acids Res. 37, D423-D430
   Abstract »    Full Text »    PDF »
Supply Chain Coordination and Influenza Vaccination.
S. E. Chick, H. Mamani, and D. Simchi-Levi (2008)
Operations Research 56, 1493-1506
   Abstract »    PDF »
Analysis of Integrated Virological and Epidemiological Reports of Norovirus Outbreaks Collected within the Foodborne Viruses in Europe Network from 1 July 2001 to 30 June 2006.
A. Kroneman, L. Verhoef, J. Harris, H. Vennema, E. Duizer, Y. van Duynhoven, J. Gray, M. Iturriza, B. Bottiger, G. Falkenhorst, et al. (2008)
J. Clin. Microbiol. 46, 2959-2965
   Abstract »    Full Text »    PDF »
A Maximum Likelihood Method for Detecting Directional Evolution in Protein Sequences and Its Application to Influenza A Virus.
S. L. Kosakovsky Pond, A. F.Y. Poon, A. J. Leigh Brown, and S. D.W. Frost (2008)
Mol. Biol. Evol. 25, 1809-1824
   Abstract »    Full Text »    PDF »
Interim Within-Season Estimate of the Effectiveness of Trivalent Inactivated Influenza Vaccine--Marshfield, Wisconsin, 2007-08 Influenza Season.
(2008)
JAMA 299, 2381-2384
   Full Text »    PDF »
Homologous Recombination Is Very Rare or Absent in Human Influenza A Virus.
M. F. Boni, Y. Zhou, J. K. Taubenberger, and E. C. Holmes (2008)
J. Virol. 82, 4807-4811
   Abstract »    Full Text »    PDF »
The Global Circulation of Seasonal Influenza A (H3N2) Viruses.
C. A. Russell, T. C. Jones, I. G. Barr, N. J. Cox, R. J. Garten, V. Gregory, I. D. Gust, A. W. Hampson, A. J. Hay, A. C. Hurt, et al. (2008)
Science 320, 340-346
   Abstract »    Full Text »    PDF »
The molecular epidemiology of influenza viruses: a lesson from a highly epidemic season.
P D'Agaro, T Rossi, P Burgnich, G D. Molin, N Coppola, G Rocco, and C Campello (2008)
J. Clin. Pathol. 61, 355-360
   Abstract »    Full Text »    PDF »
Antigenic Profile of Avian H5N1 Viruses in Asia from 2002 to 2007.
W. L. Wu, Y. Chen, P. Wang, W. Song, S.-Y. Lau, J. M. Rayner, G. J. D. Smith, R. G. Webster, J. S. M. Peiris, T. Lin, et al. (2008)
J. Virol. 82, 1798-1807
   Abstract »    Full Text »    PDF »
Bioinformatics models for predicting antigenic variants of influenza A/H3N2 virus.
Y.-C. Liao, M.-S. Lee, C.-Y. Ko, and C. A. Hsiung (2008)
Bioinformatics 24, 505-512
   Abstract »    Full Text »    PDF »
Genetic Analysis of Influenza A/H3N2 and A/H1N1 Viruses Circulating in Vietnam from 2001 to 2006.
D. Li, R. Saito, M. T. Q. Le, H. L. K. Nguyen, Y. Suzuki, Y. Shobugawa, D. T. Dinh, P. V. M. Hoang, H. T. T. Tran, H. K. Nghiem, et al. (2008)
J. Clin. Microbiol. 46, 399-405
   Abstract »    Full Text »    PDF »
BioHealthBase: informatics support in the elucidation of influenza virus host pathogen interactions and virulence.
B. Squires, C. Macken, A. Garcia-Sastre, S. Godbole, J. Noronha, V. Hunt, R. Chang, C. N. Larsen, E. Klem, K. Biersack, et al. (2008)
Nucleic Acids Res. 36, D497-D503
   Abstract »    Full Text »    PDF »
Networks of genomic co-occurrence capture characteristics of human influenza A (H3N2) evolution.
X. Du, Z. Wang, A. Wu, L. Song, Y. Cao, H. Hang, and T. Jiang (2008)
Genome Res. 18, 178-187
   Abstract »    Full Text »    PDF »
Patterns of antigenic diversity and the mechanisms that maintain them.
M. Lipsitch and J. J O'Hagan (2007)
J R Soc Interface 4, 787-802
   Abstract »    Full Text »    PDF »
Alterations in Receptor Binding Properties of Recent Human Influenza H3N2 Viruses Are Associated with Reduced Natural Killer Cell Lysis of Infected Cells.
R. E. Owen, E. Yamada, C. I. Thompson, L. J. Phillipson, C. Thompson, E. Taylor, M. Zambon, H. M. I. Osborn, W. S. Barclay, and P. Borrow (2007)
J. Virol. 81, 11170-11178
   Abstract »    Full Text »    PDF »
A Likelihood-based Index of Protein Protein Binding Affinities with Application to Influenza HA Escape from Antibodies.
T. Watabe, H. Kishino, L. de Oliveira Martins, and Y. Kitazoe (2007)
Mol. Biol. Evol. 24, 1627-1638
   Abstract »    Full Text »    PDF »
The Genesis and Spread of Reassortment Human Influenza A/H3N2 Viruses Conferring Adamantane Resistance.
L. Simonsen, C. Viboud, B. T. Grenfell, J. Dushoff, L. Jennings, M. Smit, C. Macken, M. Hata, J. Gog, M. A. Miller, et al. (2007)
Mol. Biol. Evol. 24, 1811-1820
   Abstract »    Full Text »    PDF »
Infection dynamics: from organ to host population.
T.J McKinley and J. Wood (2007)
J R Soc Interface 4, 583-586
   Abstract »    Full Text »    PDF »
The generation of influenza outbreaks by a network of host immune responses against a limited set of antigenic types.
M. Recker, O. G. Pybus, S. Nee, and S. Gupta (2007)
PNAS 104, 7711-7716
   Abstract »    Full Text »    PDF »
Antigenic and Genetic Evolution of Swine Influenza A (H3N2) Viruses in Europe.
J. C. de Jong, D. J. Smith, A. S. Lapedes, I. Donatelli, L. Campitelli, G. Barigazzi, K. Van Reeth, T. C. Jones, G. F. Rimmelzwaan, A. D. M. E. Osterhaus, et al. (2007)
J. Virol. 81, 4315-4322
   Abstract »    Full Text »    PDF »
Simultaneous amino acid substitutions at antigenic sites drive influenza A hemagglutinin evolution.
A. C.-C. Shih, T.-C. Hsiao, M.-S. Ho, and W.-H. Li (2007)
PNAS 104, 6283-6288
   Abstract »    Full Text »    PDF »
Adaptation of a Diverse Simian Immunodeficiency Virus Population to a New Host Is Revealed through a Systematic Approach to Identify Amino Acid Sites under Selection.
T. H. Vanderford, L. J. Demma, M. B. Feinberg, S. I. Staprans, and J. M. Logsdon Jr (2007)
Mol. Biol. Evol. 24, 660-669
   Abstract »    Full Text »    PDF »
The reinfection threshold regulates pathogen diversity: the case of influenza.
D. Gokaydin, J. B Oliveira-Martins, I. Gordo, and M. G. M Gomes (2007)
J R Soc Interface 4, 137-142
   Abstract »    Full Text »    PDF »
Vaccination and the dynamics of immune evasion.
O. Restif and B. T Grenfell (2007)
J R Soc Interface 4, 143-153
   Abstract »    Full Text »    PDF »
Influenza virus targets the mRNA export machinery and the nuclear pore complex.
N. Satterly, P.-L. Tsai, J. van Deursen, D. R. Nussenzveig, Y. Wang, P. A. Faria, A. Levay, D. E. Levy, and B. M. A. Fontoura (2007)
PNAS 104, 1853-1858
   Abstract »    Full Text »    PDF »
Using a Resequencing Microarray as a Multiple Respiratory Pathogen Detection Assay.
B. Lin, K. M. Blaney, A. P. Malanoski, A. G. Ligler, J. M. Schnur, D. Metzgar, K. L. Russell, and D. A. Stenger (2007)
J. Clin. Microbiol. 45, 443-452
   Abstract »    Full Text »    PDF »
An RNA conformational shift in recent H5N1 influenza A viruses.
A. P. Gultyaev, H. A. Heus, and R. C. L. Olsthoorn (2007)
Bioinformatics 23, 272-276
   Abstract »    Full Text »    PDF »
Epochal Evolution Shapes the Phylodynamics of Interpandemic Influenza A (H3N2) in Humans.
K. Koelle, S. Cobey, B. Grenfell, and M. Pascual (2006)
Science 314, 1898-1903
   Abstract »    Full Text »    PDF »
Annual influenza vaccination in community-dwelling elderly individuals and the risk of lower respiratory tract infections or pneumonia..
B. C. G. Voordouw, M. C. J. M. Sturkenboom, J. P. Dieleman, T. Stijnen, J. van der Lei, and B. H. C. Stricker (2006)
Arch Intern Med 166, 1980-1985
   Abstract »    Full Text »    PDF »
Longitudinal analysis of genotype distribution of influenza a virus from 2003 to 2005..
A. Mak, R. Rahmanian, V. Lei, D. Lawrence, M. Krajden, R. C. Brunham, D. Skowronski, Y. Li, T. Booth, S. H. Goh, et al. (2006)
J. Clin. Microbiol. 44, 3583-3588
   Abstract »    Full Text »    PDF »
Natural Selection on the Influenza Virus Genome.
Y. Suzuki (2006)
Mol. Biol. Evol. 23, 1902-1911
   Abstract »    Full Text »    PDF »
Robust Sequence Selection Method Used To Develop the FluChip Diagnostic Microarray for Influenza Virus..
M. Mehlmann, E. D. Dawson, M. B. Townsend, J. A. Smagala, C. L. Moore, C. B. Smith, N. J. Cox, R. D. Kuchta, and K. L. Rowlen (2006)
J. Clin. Microbiol. 44, 2857-2862
   Abstract »    Full Text »    PDF »
Epidemic dynamics and antigenic evolution in a single season of influenza A.
M. F Boni, J. R Gog, V. Andreasen, and M. W Feldman (2006)
Proc R Soc B 273, 1307-1316
   Abstract »    Full Text »    PDF »
The Hypervariable Immunodominant NP418-426 Epitope from the Influenza A Virus Nucleoprotein Is Recognized by Cytotoxic T Lymphocytes with High Functional Avidity..
A. C. M. Boon, G. de Mutsert, R. A. M. Fouchier, A. D. M. E. Osterhaus, and G. F. Rimmelzwaan (2006)
J. Virol. 80, 6024-6032
   Abstract »    Full Text »    PDF »
Predictability and preparedness in influenza control..
D. J. Smith (2006)
Science 312, 392-394
   Abstract »    Full Text »    PDF »
Synchrony, Waves, and Spatial Hierarchies in the Spread of Influenza.
C. Viboud, O. N. Bjornstad, D. L. Smith, L. Simonsen, M. A. Miller, and B. T. Grenfell (2006)
Science 312, 447-451
   Abstract »    Full Text »    PDF »
Patterns of Influenza-associated Mortality among US Elderly by Geographic Region and Virus Subtype, 1968-1998.
S. K. Greene, E. L. Ionides, and M. L. Wilson (2006)
Am. J. Epidemiol. 163, 316-326
   Abstract »    Full Text »    PDF »
Molecular Evolution of Human Influenza A/H3N2 Virus in Asia and Europe from 2001 to 2003.
X. S. Chi, T. V. Bolar, P. Zhao, J. S. Tam, R. Rappaport, and S.-M. Cheng (2005)
J. Clin. Microbiol. 43, 6130-6132
   Abstract »    Full Text »    PDF »
Protection of Mice against Lethal Infection with Highly Pathogenic H7N7 Influenza A Virus by Using a Recombinant Low-Pathogenicity Vaccine Strain.
E. de Wit, V. J. Munster, M. I. J. Spronken, T. M. Bestebroer, C. Baas, W. E. P. Beyer, G. F. Rimmelzwaan, A. D. M. E. Osterhaus, and R. A. M. Fouchier (2005)
J. Virol. 79, 12401-12407
   Abstract »    Full Text »    PDF »
New A/H3N2 Influenza Variant: a Small Genetic Evolution but a Heavy Burden on the Italian Population during the 2004-2005 Season.
F. Ansaldi, G. Icardi, R. Gasparini, C. Campello, S. Puzelli, A. Bella, I. Donatelli, S. Salmaso, and P. Crovari (2005)
J. Clin. Microbiol. 43, 3027-3029
   Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)