Abstract
Avian influenza viruses undergo frequent genetic reassortment, which can coincide with phenotypic changes in transmission, pathogenicity, and host species niche. Since 2020, clade 2.3.4.4b H5 high pathogenicity avian influenza viruses (HPAIVs) have driven a global panzootic, causing mass mortality in wild birds, poultry, and, for the first time, repeated spillover infections in a variety of mammalian species. This worldwide resurgence of H5 HPAIV has coincided with a dramatic increase in the number of circulating reassortant strains; however, the scale, impact and drivers of these reassortants remain unclear. Here, we combined statistical and phylodynamic modelling to reconstruct the global evolutionary dynamics of H5Nx viruses across four epizootic seasons (2020-2024). We identified 209 genetically distinct reassortants, stratified into three transmission categories based on their phylogenetic and epidemiological profiles. Accounting for sampling depth and HPAIV incidence, we estimated that reassortants emerged most frequently from Asia, but `major' reassortants associated with increased host range, inter-seasonal persistence, and long-range dissemination, more frequently emerged from Europe. Altogether, reassortant emergence followed an episodic pattern in which most reassortants were transient, but 2% seeded large clusters of secondary reassortants soon after their own emergence. Statistical modelling revealed that reassortant success was strongly shaped by ecological factors, including sustained circulation in specific wild bird orders and detection across a wider range of host niches. Collectively, our findings uncover global reassortment dynamics in H5 HPAIVs and identify key virological and ecological drivers underpinning the emergence and spread of successful reassortants. These insights support the importance of enhanced surveillance to track evolution of H5 HPAIV and identify traits relevant for consideration in pandemic risk assessment.
Competing Interest Statement
The authors have declared no competing interest.
Funder Information Declared
Biotechnology and Biological Sciences Research Council, BB/V011286/1, BB/X006204/1, BB/X006166/1, BB/Y007271/1, BB/Y007298/1
Biotechnology and Biological Sciences Research Council - Institute Strategic Grants, BBS/E/RL/230002C, BBS/E/RL/230002D
Medical Research Council, MR/Y015045/1, MR/Y03368X/1
National Natural Science Foundation of China, https://ror.org/01h0zpd94, 32061123001, 32425053, 32200416
National Key Research and Development Program of China, 2023YFC2307500, 2024YFE0106000
European Union, 727922, 874850, 101094685, 101084171, 874735
Fonds National de la Recherche Scientifique, F.4515.22
Fonds voor Wetenschappelijk Onderzoek — Vlaanderen, G098321N
Source:
Link: https://www.biorxiv.org/content/10.1101/2025.07.19.665680v2
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