The Evolutionary Genetics and Emergence of Avian Influenza Viruses in Wild Birds

Abstract

We surveyed the genetic diversity among avian influenza virus (AIV) in wild birds, comprising 167 complete viral genomes from 14 bird species sampled in four locations across the United States. These isolates represented 29 type A influenza virus hemagglutinin (HA) and neuraminidase (NA) subtype combinations, with up to 26% of isolates showing evidence of mixed subtype infection. Through a phylogenetic analysis of the largest data set of AIV genomes compiled to date, we were able to document a remarkably high rate of genome reassortment, with no clear pattern of gene segment association and occasional inter-hemisphere gene segment migration and reassortment. From this, we propose that AIV in wild birds forms transient “genome constellations,” continually reshuffled by reassortment, in contrast to the spread of a limited number of stable genome constellations that characterizes the evolution of mammalian-adapted influenza A viruses.

Spread and Persistence of Influenza A Viruses in Waterfowl Hosts in the North American Mississippi Migratory Flyway

“…A 1% cutoff reduced our variance among matching AIV segments by an order of magnitude (compared to a 99% identity score) and allowed for various levels of nucleotide identity for each independently evolving gene segment (70). Note that while we acknowledge that phylogenetic distances (i.e., patristic distances) (71) may be a more appropriate measure of relationships among viruses, these distances are still subject to arbitrary cutoff values and make measurements of reassortment more difficult (72).…”

Genome packaging in influenza A virus

“…Genome segmentation clearly plays a major role in influenza virus evolution, both within a single host species and in facilitating jumps in host range (Dugan et al, 2008;Garten et al, 2009;Hatchette et al, 2004;Kuiken et al, 2006;Nelson & Holmes, 2007;Smith et al, 2009). As discussed above, although the strategy of a divided genomic structure confers fitness benefits, it comes at the direct cost of increasing the complexity of virus assembly.…”

“…Gog et al, 2007;Hutchinson et al, 2008;Marsh et al, 2008) and yet in other circumstances, selection of efficient packaging signals from a pool of randomized sequences reveals no clear consensus sequence (Fujii et al, 2009;Ozawa et al, 2009). Similarly, reassortment in nature seems readily capable of bringing together segments from diverged genetic backgrounds that could, on occasion, include changes to packaging signals (Dugan et al, 2008;Ghedin et al, 2009;Hatchette et al, 2004). This discrepancy lacks a molecular explanation at present, but it provides further evidence that the virus tolerates a degree of imprecision in its packaging mechanism.…”

“…However (to end on a speculative note), we wonder if an imperfect packing strategy is actually beneficial to virus fitness, by providing flexibility for reassortment. Studies of natural isolates suggest that widespread and continuous reassortment events drive influenza virus evolution (Dugan et al, 2008;Ghedin et al, 2009;Hatchette et al, 2004), and in this respect the ability to package evolutionarily diverged segments would carry benefits. As well as increasing the selective advantage that the rudimentary sexual process of reassortment provides to the virus, this can perhaps be viewed in terms of selection acting on individual segments.…”

Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards

“…IAV infection in waterfowl is mainly gastrointestinal and generates very limited symptoms (1,4). In contrast to mammalian IAVs, where relatively limited numbers of subtypes circulate, avian viruses are genetically variable, with multiple subtype combinations cocirculating and with a high rate of genome reassortment (1,5). At the interface between wild and domesticated waterfowl, poultry, swine, and humans, new IAV strains evolve.…”