Parallel Evolution and the Emergence of Highly Pathogenic Avian Influenza A Viruses

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Surveillance of avian influenza is crucial for early detection of outbreaks in bird populations. Although virulent phenotypes are complex traits, several molecular determinants of virulence have been well characterised, such as a polybasic proteolytic cleavage site within the Hemagglutinin (HA) protein that allows a systemic spread of the infection. We hypothesise that the parallel evolution of highly pathogenic viral lineages from low-pathogenic ancestors may have been facilitated by permissive or compensatory secondary mutations occurring anywhere in the viral genome. We developed a computational method to detect mutations associated to an evolving trait within a given phylogeny (in this case, virulence) and applied it to a phylogenetically informed sample dataset of H7NX viruses (n>300). A panel of over 30 sites strongly associated with the HP phenotype were detected. This panel may function as an early detection system for transitions between LP to HP avian viruses.