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.