Frequency of influenza H3N2 intra-subtype reassortment: attributes and implications of reassortant spread.

Irina Maljkovic Berry,In-Kyu Yoon,Gary T Brice,Robert Kuschner,Stephen J Thomas,Melanie C Melendrez,Anthony W Hawksworth,Leslie D Edwards,Eric S Halsey,Tao Li,Patrick J Blair,Xiaoxu Lin,Stefan Fernandez,Maya Williams,Richard G Jarman

doi:10.1186/s12915-016-0337-3

Abstract

BackgroundIncreasing evidence suggests that influenza reassortment not only contributes to the emergence of new human pandemics but also plays an important role in seasonal influenza epidemics, disease severity, evolution, and vaccine efficacy. We studied this process within 2091 H3N2 full genomes utilizing a combination of the latest reassortment detection tools and more conventional phylogenetic analyses.ResultsWe found that the amount of H3N2 intra-subtype reassortment depended on the number of sampled genomes, occurred with a steady frequency of 3.35%, and was not affected by the geographical origins, evolutionary patterns, or previous reassortment history of the virus. We identified both single reassortant genomes and reassortant clades, each clade representing one reassortment event followed by successful spread of the reassorted variant in the human population. It was this spread that was mainly responsible for the observed high presence of H3N2 intra-subtype reassortant genomes. The successfully spread variants were generally sampled within one year of their formation, highlighting the risk of their rapid spread but also presenting an opportunity for their rapid detection. Simultaneous spread of several different reassortant lineages was observed, and despite their limited average lifetime, second and third generation reassortment was detected, as well as reassortment between viruses belonging to different vaccine-associated clades, likely displaying differing antigenic properties. Some of the spreading reassortants remained confined to certain geographical regions, while others, sharing common properties in amino acid positions of the HA, NA, and PB2 segments, were found throughout the world.ConclusionsDetailed surveillance of seasonal influenza reassortment patterns and variant properties may provide unique information needed for prediction of spread and construction of future influenza vaccines.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-016-0337-3) contains supplementary material, which is available to authorized users.

Highlights

Increasing evidence suggests that influenza reassortment contributes to the emergence of new human pandemics and plays an important role in seasonal influenza epidemics, disease severity, evolution, and vaccine efficacy
Reassortment identification reveals the extent of its complexity The dataset used in this study comprises 2091 H3N2 full genomes sampled from 56 different countries between 2008 and 2014
Identification of reassortment was performed by combined MrBayes/Graph-incompatibility-based Reassortment Finder (GiRaF) and Maximum likelihood (ML) analyses of segment tree incongruence, where reassortant genomes found in MrBayes/GiRaF analyses were mapped onto the ML segment trees, and the results were used for confirmation of reassortment

Summary

Introduction

Increasing evidence suggests that influenza reassortment contributes to the emergence of new human pandemics and plays an important role in seasonal influenza epidemics, disease severity, evolution, and vaccine efficacy. We studied this process within 2091 H3N2 full genomes utilizing a combination of the latest reassortment detection tools and more conventional phylogenetic analyses. The emergence and evolution of pandemic influenza has been greatly shaped by the process of segment reassortment occurring between different influenza subtypes, a process that enables swift changes of viral antigenic properties and may generate variants to which there is little to no immunity in the general population [2,3,4]. Despite high estimates of influenza reassortment capability, relatively few inter-subtype reassortants have established sustained human infections [7, 10,11,12,13]

Methods

Results

Discussion

Conclusion