Whole genome sequencing of influenza B virus isolates from a prospective household cohort

Influenza B virus undergoes seasonal antigenic drift more slowly than influenza A, but the reasons for this are unclear. While the evolutionary dynamics of influenza virus play out globally, they are fundamentally driven by mutation, reassortment, drift, and selection at the level of individual hosts. These processes have recently been described for influenza A virus, but little is known about the evolutionary dynamics of influenza B virus (IBV) within at the level of individual infections and transmission events. Here, we define the within-host evolutionary dynamics of influenza B virus by sequencing samples from natural infections from individuals in a prospective, community-based cohort. With high depth-of-coverage sequencing data from 99 upper respiratory samples collected over 8176 person-years of observation, we find that influenza B accumulates lower genetic diversity than influenza A during acute infections, reflecting its slower mutation rate. Consistent with studies of influenza A, influenza B within-host evolution is characterized by purifying selection and a lack of widespread positive selection of within-host variants. With data from 15 sequence-validated within-household transmission pairs, we estimate a tight transmission bottleneck similar to that of influenza A. These patterns of local-scale evolution are consistent with influenza B's slower global evolutionary rate.

乙型流感病毒（Influenza B virus）的季节性抗原漂移速率慢于甲型流感病毒，但其背后的原因尚未阐明。尽管流感病毒的进化动态呈现全球性分布，但其本质上由单个宿主层面的突变、重配、漂移与选择过程所驱动。这些过程近年已在甲型流感病毒中得到详细阐释，但针对乙型流感病毒（Influenza B virus, IBV）在个体感染与传播事件层面的进化动态，目前仍知之甚少。本研究依托一项前瞻性社区队列研究，对自然感染个体的样本进行测序，以此阐明乙型流感病毒的宿主内进化动态。本研究利用8176人年随访期间采集的99份上呼吸道样本的高深度测序数据，发现急性感染期内乙型流感病毒的遗传多样性积累水平低于甲型流感病毒，这与其较慢的突变率相符。与甲型流感病毒的相关研究结果一致，乙型流感病毒的宿主内进化以纯化选择为主要特征，且未出现宿主内变异的广泛正向选择现象。通过对15对经序列验证的家庭内传播配对样本进行分析，本研究估算得到的传播瓶颈效应强度与甲型流感病毒相近。上述局部尺度的进化模式与乙型流感病毒较慢的全球进化速率相一致。