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Evolution of the North American Lineage H7 Avian Influenza Viruses in Association with H7 Virus’s Introduction to Poultry

Wild bird-origin H7 subtype avian influenza viruses are a constant threat to commercial poultry, both directly by the disease they cause and indirectly through trade restrictions that can be imposed when the virus is detected in poultry. It is important to understand the genetic basis of why the North American lineage H7 viruses have repeatedly crossed the species barrier from wild birds to poultry. ABSTRACT The incursions of H7 subtype low-pathogenicity avian influenza virus (LPAIV) from wild birds into poultry and its mutations to highly pathogenic avian influenza virus (HPAIV) have been an ongoing concern in North America. Since 2000, 10 phylogenetically distinct H7 virus outbreaks from wild birds have been detected in poultry, six of which mutated to HPAIV. To study the molecular evolution of the H7 viruses that occurs when changing hosts from wild birds to poultry, we performed analyses of the North American H7 hemagglutinin (HA) genes to identify amino acid changes as the virus circulated in wild birds from 2000 to 2019. Then, we analyzed recurring HA amino acid changes and gene constellations of the viruses that spread from wild birds to poultry. We found six HA amino acid changes occurring during wild bird circulation and 10 recurring changes after the spread to poultry. Eight of the changes were in and around the HA antigenic sites, three of which were supported by positive selection. Viruses from each H7 outbreak had a unique genotype, with no specific genetic group associated with poultry outbreaks or mutation to HPAIV. However, the genotypes of the H7 viruses in poultry outbreaks tended to contain minor genetic groups less observed in wild bird H7 viruses, suggesting either a biased sampling of wild bird AIVs or a tendency of having reassortment with minor genetic groups prior to the virus’s introduction to poultry. IMPORTANCE Wild bird-origin H7 subtype avian influenza viruses are a constant threat to commercial poultry, both directly by the disease they cause and indirectly through trade restrictions that can be imposed when the virus is detected in poultry. It is important to understand the genetic basis of why the North American lineage H7 viruses have repeatedly crossed the species barrier from wild birds to poultry. We examined the amino acid changes in the H7 viruses associated with poultry outbreaks and tried to determine gene reassortment related to poultry adaptation and mutations to HPAIV. The findings in this study increase the understanding of the evolutionary pathways of wild bird AIV before infecting poultry and the HA changes associated with adaptation of the virus in poultry.