title: Evolution of the hemagglutinin expressed by human influenza A(H1N1)pdm09 and A(H3N2) viruses circulating between 2008-2009 and 2013-2014 in Germany.
abstract: This report describes the evolution of the influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in Germany between 2008-2009 and 2013-2014. The phylogenetic analysis of the hemagglutinin (HA) genes of both subtypes revealed similar evolution of the HA variants that were also seen worldwide with minor exceptions. The analysis showed seven distinct HA clades for A(H1N1)pdm09 and six HA clades for A(H3N2) viruses. Herald strains of both subtypes appeared sporadically since 2008-2009. Regarding A(H1N1)pdm09, herald strains of HA clade 3 and 4 were detected late in the 2009-2010 season. With respect to A(H3N2), we found herald strains of HA clade 3, 4 and 7 between 2009 and 2012. Those herald strains were predominantly seen for minor and not for major HA clades. Generally, amino acid substitutions were most frequently found in the globular domain, including substitutions near the antigenic sites or the receptor binding site. Differences between both influenza A subtypes were seen with respect to the position of the indicated substitutions in the HA. For A(H1N1)pdm09 viruses, we found more substitutions in the stem region than in the antigenic sites. In contrast, in A(H3N2) viruses most changes were identified in the major antigenic sites and five changes of potential glycosylation sites were identified in the head of the HA monomer. Interestingly, we found in seasons with less influenza activity a relatively high increase of substitutions in the head of the HA in both subtypes. This might be explained by the fact that mutations under negative selection are subsequently compensated by secondary mutations to restore important functions e.g. receptor binding properties. A better knowledge of basic evolution strategies of influenza viruses will contribute to the refinement of predictive mathematical models for identifying novel antigenic drift variants.
authors.affiliation: Division of Influenza Viruses and other Respiratory Viruses, National Reference Centre for Influenza, Robert Koch-Institute, Seestrasse 10, 13353 Berlin, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Wedde
authors.affiliation: Division of Influenza Viruses and other Respiratory Viruses, National Reference Centre for Influenza, Robert Koch-Institute, Seestrasse 10, 13353 Berlin, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Biere
authors.affiliation: Division of Influenza Viruses and other Respiratory Viruses, National Reference Centre for Influenza, Robert Koch-Institute, Seestrasse 10, 13353 Berlin, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wolff
authors.affiliation: Division of Influenza Viruses and other Respiratory Viruses, National Reference Centre for Influenza, Robert Koch-Institute, Seestrasse 10, 13353 Berlin, Germany. Electronic address: schweigerb@rki.de.
authors.forename: Brunhilde
authors.initials: B
authors.lastname: Schweiger
mesh_terms: D019943:Amino Acid Substitution; D016000:Cluster Analysis; D019143:Evolution, Molecular; D014644:Genetic Variation; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D053122:Influenza A Virus, H3N2 Subtype / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D017385:Sequence Homology
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus
keywords: A(H1N1)pdm09; A(H3N2); Antigenic site; Hemagglutinin; Herald strain; Receptor binding site