The evolutionary dynamics of human influenza B virus

Abstract

Despite their close phylogenetic relationship, type A and B influenza viruses exhibit major epidemiological differences in humans, with the latter both less common and less often associated with severe disease. However, it is unclear what processes determine the evolutionary dynamics of influenza B virus, and how influenza viruses A and B interact at the evolutionary scale. To address these questions we inferred the phylogenetic history of human influenza B virus using complete genome sequences for which the date (day) of isolation was available. By comparing the phylogenetic patterns of all eight viral segments we determined the occurrence of segment reassortment over a 30-year sampling period. An analysis of rates of nucleotide substitution and selection pressures revealed sporadic occurrences of adaptive evolution, most notably in the viral hemagglutinin and compatible with the action of antigenic drift, yet lower rates of overall and nonsynonymous nucleotide substitution compared to influenza A virus. Overall, these results led us to propose a model in which evolutionary changes within and between the antigenically distinct 'Yam88' and 'Vic87' lineages of influenza B virus are the result of changes in herd immunity, with reassortment continuously generating novel genetic variation. Additionally, we suggest that the interaction with influenza A virus may be central in shaping the evolutionary dynamics of influenza B virus, facilitating the shift of dominance between the Vic87 and the Yam88 lineages.

Fig. 1

Maximum a posteriori (MAP) tree of the influenza B virus HA1 domain based on 214 sequences sampled annually between 1970 and 2006. Dominant antigenic clusters (names in roman font) within the Vic87 lineage are shaded green, while those in the Yam88 lineage are shaded pink. Open blocks denote viral clusters that did not dominate in the United States. The appearances of clades related to reassortment are represented by different colored branches on the tree, as are the two antigenically distinct clades (B/Beijing/184/93-like and B/Malaysia/2506/04-like viruses) whose appearance is not related to reassortment. Representative vaccine strains are also shown. The numbers of amino acid substitutions are given next to the internal branches of both the Vic87 and the Yam88 lineages. The prevalence of influenza B virus in the United States is also shown; data taken from Viboud et al. (2006b) and updated with data from the CDC Web site (http://www.cdc.gov/flu/weekly/fluactivity.htm) (see Supplementary Material)

Fig. 2

Reassortment among the major clades of influenza B viruses. The phylogenetic background for this representation of evolutionary history is those viral clades identified in the HA1 tree shown in Fig. 1. The curved lines without arrows indicate a direct ancestor-descendent relationship (i.e., without reassortment) between viruses in the HA1 tree, while the lines with arrows depict reassortment events, with the names of new segments also listed. Due to uncertainty in some of the segment phylogenies, it is not possible to fully determine the ancestry of all reassortment events. Genome compositions (that is, the origin of the eight segments) are illustrated besides each clade by colored bars, with the order (from top to bottom) corresponding to the segment number (largest to smallest: PB2, PB1, PA, HA, NP, NA, M, NS). As the B/Victoria/02/87 (Vic87) and B/Yamagata/166/88 (Yam88) viruses fall in the same branch of the NS tree (contrary to their distinction in other gene segments), the major lineages within NS are colored differently from those in other segments. The detailed trees from which this representation was inferred are shown in Supplementary Figs. 1–8