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

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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. Influenza A viruses are an extremely divergent group of RNA viruses that infect in a variety of warm-blooded animals, including birds, horses, pigs, and humans. Since they contain a segmented RNA genome, mixed infection can lead to genetic reassortment. It is thought that the natural reservoir of influenza A viruses is the wild bird population. Influenza A viruses can switch hosts and cause novel outbreaks in new species. Influenza viruses containing genes derived from bird influenza viruses caused the last three influenza pandemics in humans. In this study, we surveyed the genetic diversity among influenza A viruses in wild birds. Through a phylogenetic analysis of the largest data set of wild bird influenza 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 influenza viruses 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.