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Published ahead of print 26 December 2013, doi: 10.1128/JVI.02163-13 JVI.02163-13
Genome-wide Analysis of Reassortment and Evolution of Human Influenza A(H3N2) Viruses Circulating between 1968 and 2011
Kim B. Westgeesta,
Colin A. Russellb,c,
Xudong Lind,e,
Monique I. J. Spronkena,
Theo M. Bestebroera,
Justin Bahlf,
Ruud van Beeka,
Eugene Skepnerb,
Rebecca A. Halpine,
Jan C. de Jonga,
Guus F. Rimmelzwaana,
Albert D.M.E. Osterhausa,
Derek J. Smitha,b,c,
David E. Wentworthd,e,
Ron A.M. Fouchiera and
Miranda de Graafa#
+ Author Affiliations
Department of Viroscience, Erasmus Medical Center, Rotterdam, Netherlandsa
Department of Zoology, University of Cambridge, Cambridge, United Kingdomb
Fogarty International Center, National Institutes of Health, Bethesda, USAc
School of Public Health, State University of New York, Albany, New York, USAd
J. Craig Venter Institute, Rockville, Maryland, USAe
Center for Infectious Diseases, The University of Texas School of Public Health, Houston, Texas, USAf
ABSTRACT
Influenza A(H3N2) viruses became widespread in humans during the 1968 H3N2 virus pandemic and have been a major cause of influenza epidemics ever since. The viruses evolve continuously by reassortment and genomic evolution. Antigenic drift is the cause for the need to update the influenza vaccine frequently. Using two datasets that span the entire period of circulation of human influenza A(H3N2) viruses, it was shown that the influenza A(H3N2) virus evolution could be mapped into thirteen antigenic clusters. Here, we have analyzed the full genome of 286 influenza A(H3N2) viruses from these two datasets to investigate the genomic evolution and reassortment patterns. Numerous reassortment events, scattered over the entire period of virus circulation, were found, but most prominently in viruses circulating between 1991 and 1998. Some of these reassortment events persisted over time, and one of these coincided with an antigenic cluster transition. Further, selection pressures and nucleotide and amino acid substitution rates of all proteins were studied, including the recently discovered PB1-N40, PA-X, PA-N155, and PA-N182 proteins. Rates of nucleotide and amino acid substitution were most pronounced for hemagglutinin, neuraminidase, and PB1-F2 proteins. Selection pressures were highest in hemagglutinin, neuraminidase, matrix 1 and non-structural protein 1. This study of genotype in relation to the antigenic phenotype throughout the entire period of circulation of human influenza A(H3N2) viruses leads to a better understanding of its evolution.
Genome-wide Analysis of Reassortment and Evolution of Human Influenza A(H3N2) Viruses Circulating between 1968 and 2011
Kim B. Westgeesta,
Colin A. Russellb,c,
Xudong Lind,e,
Monique I. J. Spronkena,
Theo M. Bestebroera,
Justin Bahlf,
Ruud van Beeka,
Eugene Skepnerb,
Rebecca A. Halpine,
Jan C. de Jonga,
Guus F. Rimmelzwaana,
Albert D.M.E. Osterhausa,
Derek J. Smitha,b,c,
David E. Wentworthd,e,
Ron A.M. Fouchiera and
Miranda de Graafa#
+ Author Affiliations
Department of Viroscience, Erasmus Medical Center, Rotterdam, Netherlandsa
Department of Zoology, University of Cambridge, Cambridge, United Kingdomb
Fogarty International Center, National Institutes of Health, Bethesda, USAc
School of Public Health, State University of New York, Albany, New York, USAd
J. Craig Venter Institute, Rockville, Maryland, USAe
Center for Infectious Diseases, The University of Texas School of Public Health, Houston, Texas, USAf
ABSTRACT
Influenza A(H3N2) viruses became widespread in humans during the 1968 H3N2 virus pandemic and have been a major cause of influenza epidemics ever since. The viruses evolve continuously by reassortment and genomic evolution. Antigenic drift is the cause for the need to update the influenza vaccine frequently. Using two datasets that span the entire period of circulation of human influenza A(H3N2) viruses, it was shown that the influenza A(H3N2) virus evolution could be mapped into thirteen antigenic clusters. Here, we have analyzed the full genome of 286 influenza A(H3N2) viruses from these two datasets to investigate the genomic evolution and reassortment patterns. Numerous reassortment events, scattered over the entire period of virus circulation, were found, but most prominently in viruses circulating between 1991 and 1998. Some of these reassortment events persisted over time, and one of these coincided with an antigenic cluster transition. Further, selection pressures and nucleotide and amino acid substitution rates of all proteins were studied, including the recently discovered PB1-N40, PA-X, PA-N155, and PA-N182 proteins. Rates of nucleotide and amino acid substitution were most pronounced for hemagglutinin, neuraminidase, and PB1-F2 proteins. Selection pressures were highest in hemagglutinin, neuraminidase, matrix 1 and non-structural protein 1. This study of genotype in relation to the antigenic phenotype throughout the entire period of circulation of human influenza A(H3N2) viruses leads to a better understanding of its evolution.
