Genome-wide evolutionary dynamics of influenza B viruses on a global scale

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.

与甲型流感病毒相比，人们对乙型流感病毒（influenza B virus）的全球规模流行病学特征及全基因组进化动态的认知仍较为匮乏。本研究构建了一套时空覆盖全面的乙型流感病毒数据集，涵盖1987年至2015年间全球采集的超过2500条病毒基因组序列，其中包含382条新测序的基因组，填补了既往分子监测研究中的大量空白。本研究新增的数据提升了欧洲、非洲及中亚地区可获取的乙型流感病毒基因组数量，优化了乙型流感病毒研究的全球研究框架。本研究揭示，山形系（Yamagata-lineage）的多样性源于两个抗原性存在差异的毒株群共同循环，且二者在全基因组层面均呈现遗传分化，未检测到系内重配的证据。与之形成对比的是，维多利亚系（Victoria-lineage）的多样性源自不同遗传进化枝的地理分隔，各进化枝的地理传播范围存在差异。两大谱系的差异体现在其抗原动态特征上：山形系病毒表现为不同抗原群交替占据主导地位的模式，而维多利亚系病毒则呈现单一谱系的抗原漂移。对乙型流感病毒基因系统发育树主干分支上的氨基酸替换进行结构定位分析，进一步验证了上述抗原差异，并揭示了两种可能影响聚合酶活性的病毒适应机制。本研究为解析全球范围内塑造乙型流感病毒进化的流行病学与分子过程提供了全新见解。