Inference of Genotype–Phenotype Relationships in the Antigenic Evolution of Human Influenza A (H3N2) Viruses

Distinguishing mutations that determine an organism's phenotype from (near-) neutral ‘hitchhikers’ is a fundamental challenge in genome research, and is relevant for numerous medical and biotechnological applications. For human influenza viruses, recognizing changes in the antigenic phenotype and a strains' capability to evade pre-existing host immunity is important for the production of efficient vaccines. We have developed a method for inferring ‘antigenic trees’ for the major viral surface protein hemagglutinin. In the antigenic tree, antigenic weights are assigned to all tree branches, which allows us to resolve the antigenic impact of the associated amino acid changes. Our technique predicted antigenic distances with comparable accuracy to antigenic cartography. Additionally, it identified both known and novel sites, and amino acid changes with antigenic impact in the evolution of influenza A (H3N2) viruses from 1968 to 2003. The technique can also be applied for inference of ‘phenotype trees’ and genotype–phenotype relationships from other types of pairwise phenotype distances.

[1]  Recommended composition of influenza virus vaccines for use in the 2003-2004 influenza season. , 2003, Releve epidemiologique hebdomadaire.

[2]  Ian A. Wilson,et al.  The structure of the influenza virus haemagglutinin glycoprotein at 3 Ã resolution , 1981 .

[3]  Yoshihiro Kawaoka,et al.  Early Alterations of the Receptor-Binding Properties of H1, H2, and H3 Avian Influenza Virus Hemagglutinins after Their Introduction into Mammals , 2000, Journal of Virology.

[4]  Ziheng Yang.  PAML 4: phylogenetic analysis by maximum likelihood. , 2007, Molecular biology and evolution.

[5]  Chao A. Hsiung,et al.  Bioinformatics models for predicting antigenic variants of influenza A/H3N2 virus , 2008, Bioinform..

[6]  Charles L. Lawson,et al.  Solving least squares problems , 1976, Classics in applied mathematics.

[7]  L. Cavalli-Sforza,et al.  PHYLOGENETIC ANALYSIS: MODELS AND ESTIMATION PROCEDURES , 1967, Evolution; international journal of organic evolution.

[8]  Trevor Hastie,et al.  The Elements of Statistical Learning , 2001 .

[9]  Colin A. Russell,et al.  The Global Circulation of Seasonal Influenza A (H3N2) Viruses , 2008, Science.

[10]  J. Taubenberger,et al.  1918 Influenza: the Mother of All Pandemics , 2006, Emerging infectious diseases.

[11]  Yi Guan,et al.  Temporally structured metapopulation dynamics and persistence of influenza A H3N2 virus in humans , 2011, Proceedings of the National Academy of Sciences.

[12]  W. Fitch.  Toward Defining the Course of Evolution: Minimum Change for a Specific Tree Topology , 1971 .

[13]  R Farber,et al.  The geometry of shape space: application to influenza. , 2001, Journal of theoretical biology.

[14]  Alice Carolyn McHardy,et al.  Allele dynamics plots for the study of evolutionary dynamics in viral populations , 2010, Nucleic Acids Res..

[15]  T. Tatusova,et al.  The Influenza Virus Resource at the National Center for Biotechnology Information , 2007, Journal of Virology.

[16]  M. Pascual,et al.  Global Migration Dynamics Underlie Evolution and Persistence of Human Influenza A (H3N2) , 2010, PLoS pathogens.

[17]  Cecile Viboud,et al.  Stochastic Processes Are Key Determinants of Short-Term Evolution in Influenza A Virus , 2006, PLoS pathogens.

[18]  I. Wilson,et al.  Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation , 1981, Nature.

[19]  Jonathan Dushoff,et al.  Hemagglutinin sequence clusters and the antigenic evolution of influenza A virus , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Robert C. Edgar,et al.  MUSCLE: multiple sequence alignment with high accuracy and high throughput. , 2004, Nucleic acids research.

[21]  Yu-Chieh Liao,et al.  Identifying potential immunodominant positions and predicting antigenic variants of influenza A/H3N2 viruses. , 2007, Vaccine.

[22]  Ron A M Fouchier,et al.  Influenza vaccine strain selection and recent studies on the global migration of seasonal influenza viruses. , 2008, Vaccine.

[23]  W. Fitch,et al.  Predicting the evolution of human influenza A. , 1999, Science.

[24]  Yoshihiro Kawaoka,et al.  Influenza Virology: Current Topics , 2006 .

[25]  A. Mchardy,et al.  The Role of Genomics in Tracking the Evolution of Influenza A Virus , 2009, PLoS pathogens.

[26]  George K. Hirst,et al.  STUDIES OF ANTIGENIC DIFFERENCES AMONG STRAINS OF INFLUENZA A BY MEANS OF RED CELL AGGLUTINATION , 1943, The Journal of experimental medicine.

[27]  Hong Jin,et al.  Two residues in the hemagglutinin of A/Fujian/411/02-like influenza viruses are responsible for antigenic drift from A/Panama/2007/99. , 2005, Virology.

[28]  Jinn-Moon Yang,et al.  Co-evolution positions and rules for antigenic variants of human influenza A/H3N2 viruses , 2009, BMC Bioinformatics.

[29]  Zhipeng Cai,et al.  A Computational Framework for Influenza Antigenic Cartography , 2010, PLoS Comput. Biol..

[30]  M. Hilleman.  Antigenic variation of influenza viruses. , 1954, Annual review of microbiology.

[31]  Recommended composition of influenza virus vaccines for use in the 2011-2012 northern hemisphere influenza season. , 2011, Releve epidemiologique hebdomadaire.

[32]  A. Lapedes,et al.  Mapping the Antigenic and Genetic Evolution of Influenza Virus , 2004, Science.

[33]  Rahul Raman,et al.  Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift , 2009, Science.

[34]  R. Webby,et al.  Replication and Transmission of H9N2 Influenza Viruses in Ferrets: Evaluation of Pandemic Potential , 2008, PloS one.

[35]  N. Bovin,et al.  Amino Acid 226 in the Hemagglutinin of H4N6 Influenza Virus Determines Binding Affinity for α2,6-Linked Sialic Acid and Infectivity Levels in Primary Swine and Human Respiratory Epithelial Cells , 2008, Journal of Virology.

[36]  Sergei L. Kosakovsky Pond,et al.  A maximum likelihood method for detecting directional evolution in protein sequences and its application to influenza A virus. , 2008, Molecular biology and evolution.

[37]  Aiping Wu,et al.  Networks of genomic co-occurrence capture characteristics of human influenza A (H3N2) evolution. , 2007, Genome research.

[38]  E. Tognotti.  Influenza pandemics: a historical retrospect. , 2009, Journal of infection in developing countries.

[39]  W. Fitch,et al.  Positive selection on the H3 hemagglutinin gene of human influenza virus A. , 1999, Molecular biology and evolution.

[40]  Derrick J. Zwickl.  Genetic algorithm approaches for the phylogenetic analysis of large biological sequence datasets under the maximum likelihood criterion , 2006 .

[41]  Wilfred Ndifon.  New methods for analyzing serological data with applications to influenza surveillance , 2009 .

[42]  M. Pagel,et al.  Bayesian estimation of ancestral character states on phylogenies. , 2004, Systematic biology.

[43]  Cecile Viboud,et al.  Phylogenetic Analysis Reveals the Global Migration of Seasonal Influenza A Viruses , 2007, PLoS pathogens.

[44]  William R. Taylor,et al.  The rapid generation of mutation data matrices from protein sequences , 1992, Comput. Appl. Biosci..

[45]  O. Gascuel,et al.  A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. , 2003, Systematic biology.

[46]  Charles L. Lawson,et al.  Solving least squares problems , 1976, Classics in applied mathematics.

[47]  Arthur Chun-Chieh Shih,et al.  Simultaneous amino acid substitutions at antigenic sites drive influenza A hemagglutinin evolution , 2007, Proceedings of the National Academy of Sciences.

[48]  M. Nei,et al.  A new method of inference of ancestral nucleotide and amino acid sequences. , 1995, Genetics.

[49]  Jun Zhu,et al.  Using a mutual information-based site transition network to map the genetic evolution of influenza A/H3N2 virus , 2009, Bioinform..