Parallel Evolution and the Emergence of Highly Pathogenic Avian Influenza A Viruses
Escalera-Zamudio M., Gutierrez B., Theze J., Russell Keown J., Carrique L., Bowden T., Pybus O.
Surveillance of avian influenza viruses is crucial for the characterization of viral diversity in bird populations. Although virulent phenotypes are complex traits, several molecular determinants of pathogenicity in avian influenza viruses have been well characterised, particularly the polybasic proteolytic cleavage site within the Hemagglutinin protein, which allows a systemic spread of the infection in avian hosts. We hypothesise that the parallel evolution of highly pathogenic lineages, from low-pathogenic ancestors, may have been facilitated by permissive or compensatory secondary mutations occurring anywhere in the viral genome. We used a comparative phylogenetic and structural approach to detect mutations across the whole genome of avian influenza viruses of the H7NX subtype, that are shared by multiple, independent highly pathogenic lineages. Parallel mutations occur frequently among highly pathogenic outbreaks. Mutations strongly associated with the HP phenotype may function as an early detection system for transitional virulence stages.