Abstract
BackgroundThe human influenza viruses undergo rapid evolution (especially in hemagglutinin (HA), a glycoprotein on the surface of the virus), which enables the virus population to constantly evade the human immune system. Therefore, the vaccine has to be updated every year to stay effective. There is a need to characterize the evolution of influenza viruses for better selection of vaccine candidates and the prediction of pandemic strains. Studies have shown that the influenza hemagglutinin evolution is driven by the simultaneous mutations at antigenic sites. Here, we analyze simultaneous or co-occurring mutations in the HA protein of human influenza A/H3N2, A/H1N1 and B viruses to predict potential mutations, characterizing the antigenic evolution.MethodsWe obtain the rules of mutation co-occurrence using association rule mining after extracting HA1 sequences and detect co-mutation sites under strong selective pressure. Then we predict the potential drifts with specific mutations of the viruses based on the rules and compare the results with the “observed” mutations in different years.ResultsThe sites under frequent mutations are in antigenic regions (epitopes) or receptor binding sites.ConclusionsOur study demonstrates the co-occurring site mutations obtained by rule mining can capture the evolution of influenza viruses, and confirms that cooperative interactions among sites of HA1 protein drive the influenza antigenic evolution.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-016-0230-5) contains supplementary material, which is available to authorized users.
Highlights
The human influenza viruses undergo rapid evolution (especially in hemagglutinin (HA), a glycoprotein on the surface of the virus), which enables the virus population to constantly evade the human immune system
The pioneering work by Smith et al [21] characterized the antigenic evolution of HA1 (A/ H3N2) based on the Hemagglutination-inhibition (HI) assays, and mapped the antigenic evolution to the phylogenetic tree based on HA1 sequences using a maximum-likelihood (ML) approach
Rules of co-occurring mutations First we look at all the available sequences of human influenza H1N1, H3N2 and B viruses in the Influenza Virus Resource database of NCBI [34] from 1918 to 2015
Summary
The human influenza viruses undergo rapid evolution (especially in hemagglutinin (HA), a glycoprotein on the surface of the virus), which enables the virus population to constantly evade the human immune system. We analyze simultaneous or co-occurring mutations in the HA protein of human influenza A/H3N2, A/H1N1 and B viruses to predict potential mutations, characterizing the antigenic evolution. The relationship between the antigenic distances based on sequences and those calculated from HI titer data was further discussed in [25], where an online tool named “nextflu” was provided for real-time tracking. Those studies have obtained insightful results, most of them focus on the clusters of antigenic mutations. Very few studies work on the interactions among site mutations in the HA proteins and their impact on the direction of antigenic evolution
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