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Cross-reactive immunity drives global oscillation and opposed alternation patterns of seasonal influenza A viruses
Type of publication
Not peer-reviewed
Publikationsform
Original article (non peer-reviewed)
Author
Gatti Lorenzo, Zhang Jitao David, Anisimova Maria, Schutten Martin, Osterhaus Albert, van der Vries Erhard,
Project
Fast joint estimation of alignment and phylogeny from genomic sequences in a frequentist framework
Show all
Original article (non peer-reviewed)
Journal
bioRxiv
Publisher
Cold Spring Harbor Laboratory
Page(s)
226613 - 226613
Title of proceedings
bioRxiv
DOI
10.1002/9780470015902.a0025545
Open Access
URL
https://www.biorxiv.org/content/early/2017/12/08/226613
Type of Open Access
Repository (Green Open Access)
Abstract
Several human pathogens exhibit distinct patterns of seasonality and circulate as pairs of discrete strains. For instance, the activity of the two co-circulating influenza A virus subtypes oscillates and peaks during winter seasons of the worlds temperate climate zones. These periods of increased activity are usually caused by a single dominant subtype. Alternation of dominant strains in successive influenza seasons makes epidemic forecasting a major challenge. From the start of the 2009 influenza pandemic we enrolled influenza A virus infected patients (n = 2,980) in a global prospective clinical study. Complete hemagglutinin (HA) sequences were obtained from 1,078 A/H1N1 and 1,033 A/H3N2 viruses and were linked to patient data. We then used phylodynamics to construct high resolution spatio-temporal phylogenetic HA trees and estimated global influenza A effective reproductive numbers (R) over time (2009-2013). We demonstrate that R, a parameter to define host immunity, oscillates around R = 1 with a clear opposed alternation pattern between phases of the A/H1N1 and A/H3N2 subtypes. Moreover, we find a similar alternation pattern for the number of global virus migration events between the sampled geographical locations. Both observations suggest a between-strain competition for susceptible hosts on a global level. Extrinsic factors that affect person-to-person transmission are a major driver of influenza seasonality, which forces influenza epidemics to coincide with winter seasons. The data presented here indicate that also cross-reactive host immunity is a key intrinsic driver of global influenza seasonality, which determines the outcome of competition between influenza A virus strains at the onset of each epidemic season.
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