Multiple introductions of equine influenza virus into the United Kingdom resulted in widespread outbreaks and lineage replacement.
Abstract: Influenza A viruses (IAVs) are prime examples of emerging viruses in humans and animals. IAV circulation in domestic animals poses a pandemic risk as it provides new opportunities for zoonotic infections. The recent emergence of H5N1 IAV in cows and subsequent spread over multiple states within the USA, together with reports of spillover infections in humans, cats and mice highlight this issue. The horse is a domestic animal in which an avian-origin IAV lineage has been circulating for >60 years. In 2018/19, a Florida Clade 1 (FC1) virus triggered one of the largest epizootics recorded in the UK, which led to the replacement of the Equine Influenza Virus (EIV) Florida Clade 2 (FC2) lineage that had been circulating in the country since 2003. We integrated geographical, epidemiological, and virus genetic data to determine the virological and ecological factors leading to this epizootic. By combining newly-sequenced EIV complete genomes derived from UK outbreaks with existing genomic and epidemiological information, we reconstructed the nationwide viral spread and analysed the global evolution of EIV. We show that there was a single EIV FC1 introduction from the USA into Europe, and multiple independent virus introductions from Europe to the UK. At the UK level, three English regions (East, West Midlands, and North-West) were the main sources of virus during the epizootic, and the number of affected premises together with the number of horses in the local area were found as key predictors of viral spread within the country. At the global level, phylogeographic analysis evidenced a source-sink model for intercontinental EIV migration, with a source population evolving in the USA and directly or indirectly seeding viral lineages into sink populations in other continents. Our results provide insight on the underlying factors that influence IAV spread in domestic animals.
Copyright: © 2025 Mojsiejczuk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Publication Date: 2025-06-09 PubMed ID: 40489557PubMed Central: PMC12236680DOI: 10.1371/journal.ppat.1013227Google Scholar: Lookup
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Summary
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Multiple introductions of equine influenza virus into the United Kingdom led to widespread outbreaks and eventual replacement of the dominant virus lineage. The study analyzed genetic and epidemiological data to understand how different virus strains spread within the UK and globally.
Background and Significance
- Influenza A viruses (IAVs) can infect both humans and various animal species and are known for their ability to emerge and adapt.
- Domestic animals, including horses, can serve as reservoirs for IAVs, with potential zoonotic transmission risks to humans and other species.
- The horse harbors a lineage of IAV of avian origin that has circulated for over 60 years, making it a valuable model for studying virus evolution and transmission.
- In 2018-2019, a Florida Clade 1 (FC1) equine influenza virus caused one of the largest outbreaks in the UK, replacing the previously circulating Florida Clade 2 (FC2) since 2003.
Research Objectives
- To understand the virological and ecological factors that contributed to the large 2018/19 equine influenza outbreak in the UK.
- To reconstruct the spread of the virus across the UK using genomic sequencing combined with epidemiological data.
- To analyze the global evolutionary patterns and migration of equine influenza viruses.
Methods
- Collection and whole genome sequencing of equine influenza virus samples from UK outbreaks during the epizootic.
- Integration of these new genomic data with existing sequences and epidemiological metadata to map viral spread.
- Phylogeographic analysis to examine the origin and international movement patterns of equine influenza viruses.
Key Findings
- The 2018/2019 outbreak was primarily due to a single introduction of the FC1 virus lineage from the USA into Europe.
- Subsequently, multiple independent introductions of the virus occurred from Europe into the UK, rather than a single entry point.
- Within the UK, three regions—East, West Midlands, and North-West England—acted as primary sources that contributed to the spread of the virus nationally.
- The likelihood of viral spread in a local area was strongly correlated with two factors: the number of infected premises and the local horse population density.
- On the global scale, a source-sink model was observed, where the USA acts as a source population for equine influenza viruses, seeding viral lineages to “sink” populations on other continents through direct or indirect transmission routes.
Implications
- The study highlights how multiple virus introductions and regional animal densities drive large-scale epizootics.
- Understanding viral spread patterns can help in developing improved surveillance, biosecurity, and control strategies in domestic animal populations.
- Insights into intercontinental virus migration emphasize the importance of monitoring virus evolution in source populations, particularly in the USA, to predict and mitigate future outbreaks.
- It also underscores the zoonotic potential inherent in IAVs circulating in domestic animals and the risk they pose to other species including humans.
Cite This Article
APA
Mojsiejczuk L, Whitlock F, Chen H, Magill C, Aranday-Cortes E, Bone J, Tong L, Da Silva Filipe A, Bryant N, Newton JR, Chambers TM, Reedy SE, Nemoto M, Yamanaka T, Hughes J, Murcia PR.
(2025).
Multiple introductions of equine influenza virus into the United Kingdom resulted in widespread outbreaks and lineage replacement.
PLoS Pathog, 21(6), e1013227.
https://doi.org/10.1371/journal.ppat.1013227 Publication
Researcher Affiliations
- MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
- MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
- Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
- MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
- MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
- MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
- MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
- MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
- MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
- Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
- Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
- Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky, United States of America.
- Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky, United States of America.
- Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
- Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
- MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
- MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
MeSH Terms
- Animals
- Horses / virology
- Orthomyxoviridae Infections / epidemiology
- Orthomyxoviridae Infections / veterinary
- Orthomyxoviridae Infections / virology
- Orthomyxoviridae Infections / transmission
- United Kingdom / epidemiology
- Horse Diseases / epidemiology
- Horse Diseases / virology
- Disease Outbreaks / veterinary
- Phylogeny
- Influenza A Virus, H3N8 Subtype / genetics
- Humans
- Influenza A virus / genetics
- Genome, Viral
Conflict of Interest Statement
The authors have declared that no competing interests exist.
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