Influenza B Viruses Exhibit Lower Within-Host Diversity than Influenza A Viruses in Human Hosts.

Andrew L Valesano,Adam S Lauring,Arnold S Monto,Emily T Martin,John T Mccrone,William J Fitzsimmons,Joshua G Petrie,Colin R Parrish

doi:10.1128/jvi.01710-19

Andrew L Valesano, Adam S Lauring + Show 6 more

Open Access

https://doi.org/10.1128/jvi.01710-19

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Abstract

Influenza B virus (IBV) undergoes seasonal antigenic drift more slowly than influenza A virus, but the reasons for this difference are unclear. While the evolutionary dynamics of influenza viruses 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 IBV during individual infections and transmission events. Here, we define the within-host evolutionary dynamics of IBV by sequencing virus populations from naturally infected individuals enrolled in a prospective, community-based cohort over 8,176 person-seasons of observation. Through analysis of high depth-of-coverage sequencing data from samples from 91 individuals with influenza B, we find that IBV accumulates lower genetic diversity than previously observed for influenza A virus during acute infections. Consistent with studies of influenza A viruses, the within-host evolution of IBVs is characterized by purifying selection and the general absence of widespread positive selection of within-host variants. Analysis of shared genetic diversity across 15 sequence-validated transmission pairs suggests that IBV experiences a tight transmission bottleneck similar to that of influenza A virus. These patterns of local-scale evolution are consistent with the lower global evolutionary rate of IBV.IMPORTANCE The evolution of influenza virus is a significant public health problem and necessitates the annual evaluation of influenza vaccine formulation to keep pace with viral escape from herd immunity. Influenza B virus is a serious health concern for children, in particular, yet remains understudied compared to influenza A virus. Influenza B virus evolves more slowly than influenza A virus, but the factors underlying this are not completely understood. We studied how the within-host diversity of influenza B virus relates to its global evolution by sequencing viruses from a community-based cohort. We found that influenza B virus populations have lower within-host genetic diversity than influenza A virus and experience a tight genetic bottleneck during transmission. Our work provides insights into the varying dynamics of influenza viruses in human infection.

Highlights

Influenza viruses rapidly mutate and evolve through selection, genetic drift, and reassortment [1]
influenza B virus (IBV) exhibits lower within-host diversity compared to influenza A virus (IAV)
We define the within-host genetic diversity of IBV in natural infections by sequencing 106 samples collected over 8176 person-seasons of observation in a household cohort

Summary

Introduction

Influenza viruses rapidly mutate and evolve through selection, genetic drift, and reassortment [1]. Influenza A virus (IAV) and influenza B virus (IBV) evolve under strong positive selection driven by pressure for escape from pre-existing population immunity [2,3]. IAV and IBV both undergo seasonal antigenic drift and share a similar genomic architecture, but their ecology and evolution differ in important ways [5]. While IBV accounts for roughly one-third of influenza’s burden of morbidity and mortality [6,7], it circulates only in humans and is considered to be a lower pandemic risk than influenza A (IAV) due to the lack of an animal reservoir. Like IAV, there are co-circulating, antigenically-distinct lineages of IBV that are included in the quadrivalent influenza vaccine. Two lineages of IBV diverged in the 1980s, B/Victoria/2/87-like and B/Yamagata/16/88-like, here referred to as B/Victoria and B/Yamagata, respectively [8]

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