Gene flow and competitive exclusion of avian influenza A virus in natural reservoir hosts

Abstract

Geographical separation of host species has shaped the avian influenza A virus gene pool into independently evolving Eurasian and American lineages, although phylogenetic evidence for gene flow and reassortment indicates that these lineages also mix on occasion. While the evolutionary dynamics of the avian influenza gene pool have been described, the consequences of gene flow on virus evolution and population structure in this system have not been investigated. Here we show that viral gene flow from Eurasia has led to the replacement of endemic avian influenza viruses in North America, likely through competition for susceptible hosts. This competition is characterized by changes in rates of nucleotide substitution and selection pressures. However, the discontinuous distribution of susceptible hosts may produce long periods of co-circulation of competing virus strains before lineage extinction occurs. These results also suggest that viral competition for host resources may be an important mechanism in disease emergence.

FIG. 1. Phylogeny of H6 and H4 HA genes

Dated MCC phylogeny of the H6 (A) and H4 (B) HA of viruses. Blue bars at nodes indicate 95% HPD of TMRCAs. Scale bar shows the time-scale in years. In (A) the grey box and dashed red lines correspond to the period when lineage A introductions into the North American gene pool occurred and clades 1–6 indicate isolates with Eurasian ancestry isolated in North American wild birds. Taxa marked indicated in red in (A) is a hemagglutinin lineage introduced with Eurasian ancestry isolated in North American wild birds. This lineage corresponds to the introduction shown in Fig 3.

FIG. 2. Bayesian skyline plots of the H6 and H4 hemagglutinin genes

(A) Changes in genetic diversity of H6 subtype viruses isolated over the last thirty years from North American wild birds. A measure of genetic diversity is given with the 95% HPD indicated by blue lines. The dashed red lines correspond to the period when lineage A introductions into the North American gene pool occurred. (B) Changes in genetic diversity of H6 subtype lineage A viruses size through time. (C) Changes in genetic diversity of H6 subtype lineage B viruses until time of extinction in 2002. (D) Changes in genetic diversity of H4 subtype viruses. All figures are on the same time-scale in years.

FIG. 3. Phylogeny of N1, N2, and N8 neuraminidase genes

Dated phylogenies of N1 (A), N2 (B), N3 (C) NA gene of viruses. Red branches indicate sequence data with geographical origins other than North America (i.e. Eurasian or Oceanic isolates). Blue bars at nodes indicate 95% HPD of TMRCAs. Scale bar shows the time-scale in years. Full phylogenetic trees with sequence identifiers are provided in the supplementary material (Fig. S2). The lineage indicated in the grey box in (B) is a neuraminidase lineage introduced with Eurasian ancestry isolated in North American wild birds. This lineage corresponds to the introduction number 4 (represented by gadwall/OH/37/99) shown in Fig. 1.

FIG. 4. Dated internal gene phylogenies of viruses isolated from North American and Eurasian gene pools

PB1 (A), PA (B), PB2 (C) and M (D) genes. Red branches indicate sequence data with geographical origins other than North America (i.e. Eurasian or Oceanic isolates). Blue bars at nodes indicate 95% HPD of TMRCAs. Scale bar shows the time-scale in years.