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

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.

Selection on non-antigenic gene segments of seasonal influenza A virus and its impact on adaptive evolution

“…With eight gene segments, the chance that a coinfected individual transmits a new reassortant strain would be much higher, at nearly 100 per cent, such that around 5 per cent of the infected population would be expected to carry a first-generation reassortant virus. Interestingly, this low-level reassortment is consistent with an estimated frequency of reassortment events observed among sampled virus genomes over time, at around 3.35 per cent ( Maljkovic Berry et al 2016 ). This observation, in part, could be explained by the likelihood of coinfection, and thus reassortment, being reduced as result of herd immunity—that is viral infections with novel antigenic variants are less likely to occur in individuals that have been previously infected with older antigenic variants.…”

“…selective sweeps and genetic bottlenecks) will also similarly impact the rest of the virus genome. However, whole-genome analyses of seasonal influenza A viruses indicate that reassortment is relatively frequent, with each gene segment having somewhat of a distinctive evolutionary history ( Holmes et al 2005 ; Nelson et al 2008b ; Rambaut et al 2008 ; Westgeest et al 2014 ; Maljkovic Berry et al 2016 ). Estimated differences in the times to most recent common ancestor (TMRCA) across the genome can also exceed 6 years ( Rambaut et al 2008 ), which is inconsistent with strong linkage effects solely shaping the genetic diversity patterns of this virus.…”

The Ecology and Evolution of Influenza Viruses

“…However, important examples include the appearance of H1N2 viruses detected sporadically in humans (Guo et al 1992;Xu et al 2002;Ellis et al 2003;Al Faress et al 2008). In contrast, intra-subtype reassortment occurs frequently (Holmes et al 2005;Nelson et al 2008;Rambaut et al 2008;Westgeest et al 2014;Berry et al 2016) and likely far more so than detected through phylogenetic analysis as it may involve parental lineages that are difficult to distinguish on evolutionary trees and/or the inclusion of internal gene segments often not included in analyses.…”

Population Diversity and Collective Interactions during Influenza Virus Infection

“…There are limited data on reassortment during human infection, though one study has suggested that the effective reassortment rate may be relatively low during acute infection (62). At the host population level however, reassortment appears common among circulating seasonal IAVs of the same subtype and may have played a role in increasing the severity of some seasonal epidemics (63)(64)(65)(66)(67)(68).…”