DOI: 10.5061/dryad.4qrfj6qdk
title: Ecogeographic drivers of the spatial spread of highly pathogenic avian influenza outbreaks in Europe and North America, 2016–2022

description: 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 inter-continental transport across the Atlantic Ocean is
 relatively rare. Increase in mean ambient temperature over time was
 predictive of reduced H5Nx virus spread, which may reflect the effect of
 climate change on declines in host species abundance, decreased
 persistence of the virus in the environment, or changes in migratory
 patterns due to ecological alterations. Our data provide new knowledge
 about the spread and directionality of H5Nx virus dispersal in Europe and
 North America during an actively evolving inter-continental outbreak,
 including predictors of virus movement between regions, which will
 contribute to surveillance and mitigation strategies as the outbreak
 unfolds, and in future instances of uncontained avian spread of HPAI
 viruses.
description: <em>Publicly available H5Nx sequence data and phylogenetic
 analysis</em> 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 acquisition, and 15 unpublished H5N1 HA sequences from avian surveillance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, location, or host species were
 excluded, resulting in 506 sequences. Downsampling was performed to ensure
 relative evenness of geographic state groupings while preserving genetic
 diversity of the dataset, using geographic state and year for random
 stratification. To root and historically time-calibrate the tree, H5
 subtype HA avian sequences from IRD were downloaded for the period
 1979–2015 from Europe and North America and randomly downsampled by year,
 resulting in 33 historic sequences. These sequences were ‘masked’ to
 ensure their contribution to the tree structure but not to quantification
 of diffusion rates or the GLM. The total downsampled dataset, including
 the outgroup (GISAID sequences from North America (n=170), unpublished
 Massachusetts sequences acquired by our group (n=15), publicly available
 H5Nx sequences from Europe 2016-2022 (n=162)), and historic sequences
 (n=33) resulted in a total of 380 sequences (Supplementary table 1).
 Multiple sequence alignments were performed using MUSCLE in Geneious Prime
 2022.05.14 (https://www.geneious.com) and trimmed to the open reading frame.
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