Ecogeographic drivers of the spatial spread of highly pathogenic avian influenza outbreaks in Europe and North America, 2016–2022

H5Nx highly pathogenic avian influenza (HPAI) viruses of clade 2.3.4.4 have caused outbreaks in Europe among wild and domestic birds since 2016 and were introduced to North America via wild migratory birds in December 2021. We examined the spatiotemporal extent of HPAI viruses across continents and characterize ecological and environmental predictors of virus spread between geographic regions through constructing a Bayesian phylodynamic generalized linear model (phylodynamic-GLM). Findings demonstrate localized epidemics of H5Nx throughout Europe in the first several years of the epizootic, followed by a singular branching point where H5N1 viruses were introduced to North America, likely via stopover locations throughout the North Atlantic. Once in the US, H5Nx viruses spread at a greater rate between US-based regions and no evidence demonstrated spread back to any European region. We establish that geographic proximity is a predictor of virus spread between regions, which implies that ..., Publicly available H5Nx sequence data and phylogenetic analysis
All publicly available avian-derived (domestic and wild) H5Nx HA segment sequences from Europe and North America between 2016 and 2022 were downloaded from the Influenza Research Database (IRD) on May 12, 2022 (n=321). We added 170 publicly available H5Nx HA sequences from 2021–2022 downloaded from GISAID on May 15, 2022, as these were unavailable on IRD at the time of sequence acquisition, and 15 unpublished H5N1 HA sequences from avian surveillance in Massachusetts, USA by our research group in 2022 (described elsewhere), totaling 546 HA sequences. Metadata for each sequence was collected, including sampling date, season, host species, and geographic sampling location. Only IAV sequences from wild avian species or environmental matrices were included. Duplicate sequences, sequences with less than 75% unambiguous bases, all vaccine derivative and recombinant sequences, and sequences with unavailable isolation date, locatio..., Notepad++, BEAST v.1.10.4, RStudio