A systematic review of reported reassortant viral lineages of influenza A

Abstract

Background: Most previous evolutionary studies of influenza A have focussed on genetic drift, or reassortment of specific gene segments, hosts or subtypes. We conducted a systematic literature review to identify reported claimed reassortant influenza A lineages with genomic data available in GenBank, to obtain 646 unique first-report isolates out of a possible 20,781 open-access genomes.

Results: After adjusting for correlations, only: swine as host, China, Europe, Japan and years between 1997 and 2002; remained as significant risk factors for the reporting of reassortant viral lineages. For swine H1, more reassortants were observed in the North American H1 clade compared with the Eurasian avian-like H1N1 clade. Conversely, for avian H5 isolates, a higher number of reported reassortants were observed in the European H5N2/H3N2 clade compared with the H5N2 North American clade.

Conclusions: Despite unavoidable biases (publication, database choice and upload propensity) these results synthesize a large majority of the current literature on novel reported influenza A reassortants and are a potentially useful prerequisite to inform further algorithmic studies.

Fig. 1

Decision tree applied to remove suspected duplicate strains from the unique set of FRIs identified in the literature. Data was first ranked according to whole genome sequence homology, from lowest to highest. The pairs were evaluated individually, starting with the most genetically similar through the following criteria indicated in the figure (detail provided in Methods). Numbers in red at deletion decision points indicate the number of isolates that were removed at that stage

Fig. 2

Crude (red) and adjusted (blue) odds ratios for the rate of reporting inter and intra-subtype reassortants by region (a), host (b) and year (c). The dashed line at 1.00 on a and b represents the baseline level of risk, vertical bars crossing the dashed line indicate no effect at the 5 % level. The vertical lines above and below each point indicate 95 % confidence intervals. Adjusted odds are from the general additive logistic model of region and host as factors and year of isolated as a smooth term (c) [35]. Blue areas of c show 95 % confidence interval for smooth term for the contribution to the odds from the year of isolation. The univariate analysis where year was treated as a categorical variable is presented in Additional file 1: Table S1. Blue areas of c show 95 % confidence interval for smooth term for year of isolation

Fig. 3

Maximum likelihood phylogenies and distributions of pairwise genetic similarity shown as a density of Hamming distance for H1 Swine, H5 Avian. Maximum likelihood phylogenies illustrating the phylogenetic relationship between 1 same size random sample and the FRI data for a H1 Swine and b H5 Avian. The type of data on each tree is indicated by the tip colour, red tips show FRI data and blue tips show data from 1 same sized random subset. Clustering of particular clades is indicated on the tree. Trees were mid-point rooted. Distribution of pairwise genetic similarity shown as a density of hamming distance for c H1 Swine, d H5 Avian. Isolate comparisons for each host-subtype combination from the reassorted set are indicated in red, and the median across ten same size random subsets of isolates from GenBank for each host/subtype pair is indicated in black. The grey shaded area represents the 10^th and 90^th percentile across the ten same size random subsets. Labelled phylogenies are provided in Additional File 7