Full genomes location summaryTab-delimited text file detailing locations and lineages of 2,651 full-length influenza B virus genomes in this study (Fig 1 source data).fluB_location_summary.txtFull genomes time summaryTab-delimited text file detailing year of isolation and lineage of 2,651 full-length influenza B virus genomes from this study (Fig 1 source data).fluB_timeseries_summary.txtMaximum likelihood treesCompressed file of bootstrapped ML phylogenies inferred using RAxML and used to characterise influenza B virus genotypes.maximum-likelihood-trees.zipBEAST XML filesCompressed file of BEAST input files (xml) used to infer the molecular clock phylogenies as well as ancestral reconstruction and phylodynamic analysis for influenza B virus genes.beast-xml-files.zipMaximum clade credibility (MCC) treesCompressed file comprising of BEAST output MCC trees.mcc-trees.zipSummary of genotypesTab-delimited text file detailing inferred genotypes for influenza B viruses, representing over 10,000 strains including 2,651 complete genomes.genotypes-summary.txtMCC trees annotated with trunk substitutionsCompressed file containing MCC trees for B/Yamagata HA, B/Victoria HA, B/Yamagata PB1, and B/Victoria NA annotated with inferred mutations along the trunk lineages.trunk-substitutions-mcc-trees.zipInput files for antigenic analysisCompressed file comprising of: tab-delimited HI data file, BEAST XML file for generation of set of empirical trees and XML file for running BMDS models for B/Yamagata and B/Victoria.antigenic-evolution-input.zipOutput files from antigenic analysisCompressed file containing MCC trees from BMDS analysis (source data for Figure 4) and tab-delimited file summaries of mean antigenic distance from phylogenetic root inferred across 2,000 posterior trees to calculate mean antigenic drift rates (source data for Table 2). Posterior trees files were too large (>50 MB in compressed form each) to be included.antigenic-evolution-output.zip

The global-scale epidemiology and genome-wide evolutionary dynamics of influenza B remain poorly understood compared with influenza A viruses. We compiled a spatio-temporally comprehensive dataset of influenza B viruses, comprising over 2,500 genomes sampled worldwide between 1987 and 2015, including 382 newly-sequenced genomes that fill substantial gaps in previous molecular surveillance studies. Our contributed data increase the number of available influenza B virus genomes in Europe, Africa and Central Asia, improving the global context to study influenza B viruses. We reveal Yamagata-lineage diversity results from co-circulation of two antigenically-distinct groups that also segregate genetically across the entire genome, without evidence of intra-lineage reassortment. In contrast, Victoria-lineage diversity stems from geographic segregation of different genetic clades, with variability in the degree of geographic spread among clades. Differences between the lineages are reflected in their antigenic dynamics, as Yamagata-lineage viruses show alternating dominance between antigenic groups, while Victoria-lineage viruses show antigenic drift of a single lineage. Structural mapping of amino acid substitutions on trunk branches of influenza B gene phylogenies further supports these antigenic differences and highlights two potential mechanisms of adaptation for polymerase activity. Our study provides new insights into the epidemiological and molecular processes shaping influenza B virus evolution globally.