Ecological divergence of wild birds drives avian influenza spillover and global spread

The diversity of influenza A viruses (IAV) is primarily hosted by two highly divergent avian orders: Anseriformes (ducks, swans and geese) and Charadriiformes (gulls, terns and shorebirds). Studies of IAV have historically focused on Anseriformes, specifically dabbling ducks, overlooking the diversity of hosts in nature, including gull and goose species that have successfully adapted to human habitats. This study sought to address this imbalance by characterizing spillover dynamics and global transmission patterns of IAV over 10 years at greater taxonomic resolution than previously considered. Furthermore, the circulation of viral subtypes in birds that are either host-adapted (low pathogenic H13, H16) or host-generalist (highly pathogenic avian influenza-HPAI H5) provided a unique opportunity to test and extend models of viral evolution. Using Bayesian phylodynamic modelling we uncovered a complex transmission network that relied on ecologically divergent bird hosts. The generalist subtype, HPAI H5 was driven largely by wild geese and swans that acted as a source for wild ducks, gulls, land birds, and domestic geese. Gulls were responsible for moving HPAI H5 more rapidly than any other host, a finding that may reflect their long-distance, pelagic movements and their immuno-naive status against this subtype. Wild ducks, long viewed as primary hosts for spillover, occupied an optimal space for viral transmission, contributing to geographic expansion and rapid dispersal of HPAI H5. Evidence of inter-hemispheric dispersal via both the Pacific and Atlantic Rims was detected, supporting surveillance at high latitudes along continental margins to achieve early detection. Both neutral (geographic expansion) and non-neutral (antigenic selection) evolutionary processes were found to shape subtype evolution which manifested as unique geographic hotspots for each subtype at the global scale. This study reveals how a diversity of avian hosts contribute to viral spread and spillover with the potential to improve surveillance in an era of rapid global change. Author summary Our study provides novel insights into the biology of influenza A virus (IAV), which is timely in view of the unusually large number of animal and human cases of highly pathogenic avian influenza (HPAI) H5 across Europe, Asia, Africa and North America. Currently we face challenges with predicting how the avian reservoir will influence IAV spread because the mechanisms by which different subtypes disperse are not well understood. Our study sought to address this knowledge gap by systematically comparing the evolutionary dynamics that drive IAV transmission across subtypes and bird hosts with the goal of identifying spillover pathways at the wild-domestic interface. By analyzing the evolution of IAV over 10 years at greater taxonomic resolution than previously considered, we uncovered a complex transmission network that relied on ecologically divergent bird hosts. Domestic birds were responsible for slow but steady range expansion of HPAI H5, while wild birds such as geese, swans, gulls and ducks contibuted to rapid but episodic dispersal via uniquely different pathways. By assessing how virus-host systems are coupled, findings from this study have the potential to refine and enhance global surveillance and outbreak prediction.