#18,875
Eighteen months ago (March 2024) the avian flu world was rocked when - in the space of a few days - we learned that goats in Minnesota and cattle in Texas, had both been confirmed infected with HPAI H5N1.
Although cattle had previously been successfully infected in the laboratory with older clades of HPAI H5 - and we'd seen scattered evidence that pigs could be infected - both of these events were largely unexpected (see A Brief History Of Influenza A In Cattle/Ruminants).
In May of 2024 the host range of HPAI H5N1 expanded again, as we learned that Alpacas in Idaho had been infected with the B3.13 genotype (see USDA: HPAI H5N1 Detected In Alpacas.
Many counties, including the UK, considered these spillovers to be a uniquely American problem - linked to a local genotype (B3.13) - which they deemed highly unlikely to spread to Europe (see UK HAIRS assessment).
But not everyone was convinced.
In June of 2024 Germany's FLI issued a Statement On their Experimental Infection Of Dairy Cows With A European H5N1 Virus, finding it replicated efficiently in bovine mammary tissue and could produce adaptive mutations (PB2 E627K) during replication.
In September we saw a preprint which found high levels of antibodies to H5, H7, and H9 influenza A viruses in goats and sheep in Pakistan (samples collected in 2023), all of which was highly suggestive of past infection.By late October - after more than 400 cattle herds had been infected across 14 U.S. states with the B3.13 genotype - we saw the first (limited) spillover of a new genotype D.2, into pigs in Oregon.
Three new genotypes had emerged with the fall migration (D.1, D.2, D.3), which were hitting wild birds and poultry very hard, and had produced a small number of severe illness in humans (including 1 death).
In February of this year, after 950+ B3.13 outbreaks in U.S. dairy herds, we saw the first spillover of genotype D.1 to cattle in Nevada. Ten days later, the USDA confirmed another spillover of D.1 to cattle in Arizona.
In March of this year, the UK announced their first H5N1 Detection In a Domestic Sheep, which was followed in May by a report from Norway's Veterinary Institute of their First discovery of H5N1 (antibodies) in sheep in NorwaySuddenly the B3.13 genotype no longer had a monopoly on infecting cattle, putting the world on notice.
Last month we looked at a preprint on the Norway event (see Preprint: Detection of Antibodies Specific to H5 Avian Influenza Virus in a Sheep in Norway, June 2024).
Today we've got our first detailed report on the UK event published in Emerging Microbes & Infections, which identifies both the genotype (D1.2), and a small number of amino acid changes.
Two changes were identified in the HA protein (D171N and D277G); neither is associated with increased zoonotic potential, although D171N has been previously reported in genotype B3.13 H5N1 sequences from cattle in the USA and may represent a ruminant-associated adaptation (Figure 2) [Citation12,Citation50].
Additional substitutions distinguishing the sheep and avian sequences included PB2 N456D, NA L75F and V114M, PA L335F and PB1 M290 V, K577E, and Q688H.
The functional impact (if any) of these sheep-associated mutations isn't known.
While this UK case appears to have been an isolated, `dead-end' infection, the reports from Norway (and Pakistan) suggest that spillovers into sheep may be more common than we suspect.
These recent spillovers into livestock also illustrate the risks of `mixed-species' farming, particularly when biosecurity is lax.
- Poultry shed copious quantities of the H5N1 virus into the environment via feces, feathers, and water.
- Livestock (cattle, sheep, goats, pigs, alpacas) and other mammals on the same premises can be exposed via contaminated feed, bedding, and water.
- Each new infected species introduces selective pressures on the virus, which increases the chances of host-adaptive mutations.
Mixed-species farming - very much as with live poultry markets - provides novel viruses with access to new hosts, and fresh opportunities to reassort or adapt (see Study: Seroconversion of a Swine Herd in a Free-Range Rural Multi-Species Farm against HPAI H5N1 2.3.4.4b Clade Virus).
While most of these mutations will undoubtedly be evolutionary dead-ends, the virus only needs to get lucky once - while we have to stay lucky 100% of the time.
Due to its length I've only posted the abstract and some extended excerpts from today's study. Follow the link to read it in its entirety.
Detection of clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus in a sheep in Great Britain, 2025
Ashley C. Banyard, Holly Coombes, Jacob Terrey, Natalie McGinn, James Seekings, Benjamin Clifton,
Article: 2547730 | Received 27 Jun 2025, Accepted 10 Aug 2025, Published online: 15 Sep 2025
https://doi.org/10.1080/22221751.2025.2547730
ABSTRACT
Clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) continues to pose a significant global threat, affecting wild and domestic avian, and mammalian species. In early 2024, H5N1 HPAIV was detected in dairy cattle in the United States of America, where it has continued to circulate, with sporadic detections also reported in other ruminant species. The detection of high viral loads in milk from infected cattle, resulted in several human infections, underscoring the zoonotic potential of these viruses.
In response, several countries have intensified surveillance in non-avian species to evaluate the potential for undetected viral circulation in captive mammals. In Great Britain, bulk milk tank testing of cattle and targeted surveillance of captive mammalian species on an infected premises is undertaken in accordance with the outcome of a rapid risk assessment. This assessment is undertaken to determine epidemiological links between the poultry and captive mammals.
A result of this testing was the first recorded detection of clade 2.3.4.4b H5N1 HPAIV in a sheep in March 2025, identified on an infected poultry premises housing ducks, chickens, turkeys and geese in Great Britain. An initial seropositive result in a single ewe triggered further investigation, confirming serological positivity across repeated sampling and the presence of viral RNA in milk samples.
This detection was confined to a single animal and is likely attributable to proximity to infected poultry and a presumed heavily contaminated environment. The implications of this detection in a ruminant host are discussed in the context of interspecies transmission and surveillance strategies.
(SNIP)
Discussion
The detection of clade 2.3.4.4b H5N1 vRNA in a sheep represents the first reported case of infection with this virus in this species globally, and the first detection in a ruminant outside of the USA. Previous detections of clade 2.3.4.4b H5N1 in mammalian species have generally been attributed to elevated environmental infection pressure, typically associated with large-scale mortality events in wild bird populations [Citation2,Citation3].In such scenarios, transmission pathways are often apparent, particularly among scavenging species, where these mammals are presumed to have acquired infection through close contact with infected carcasses, most plausibly via the ingestion of dead or sick wild birds [Citation2, Citation3].
(SNIP)
The viral sequence obtained from the ewe provides the only definitive evidence that replication occurred within this host. Comparative genomic analysis revealed several amino acid substitutions across multiple gene segments in the virus isolated from the sheep. These changes were absent in viral sequences derived from infected birds on the same premises, which exhibited a high degree of genetic identity among themselves. This divergence strongly suggests that the virus underwent replication and genetic adaptation within the ewe, consistent with host-specific evolutionary pressure.However, the functional significance of these mutations, particularly regarding viral fitness, host range, or transmissibility, remain unknown. Further virological and in vivo studies are required to assess the potential implications of these sequence changes for cross-species transmission and adaptation.
However, this unusual detection raises the possibility of alternative routes of infection beyond the typical scavenging-behaviour related exposures. The ewe was co-located on an infected holding where chickens, ducks, and geese had tested positive for H5N1, and had been housed since December 2024 in a shed directly adjacent to the one housing both the ducks and geese (Group B).
Initial avian testing revealed widespread vRNA shedding among the birds, via both cloacal and oropharyngeal routes. Importantly, the presence of infection in Anseriformes species (ducks and geese) increases the likelihood of a heavily contaminated environment, given their known capacity for extensive environmental viral shedding [Citation30].
(SNIP)
In conclusion, this study has demonstrated that it is possible for mammalian species co-located on an infected premises to become infected with these viruses through unusual infection routes and that appropriate risk assessments and both sampling and testing of mammals in such scenarios is important to understand where infection may have occurred.A recent report found that blood samples collected in 2024 from 220 sheep, which had grazed in areas affected by dead and diseased H5N1-infected pheasants in Norway during 2023, contained antibodies against H5 AIV [Citation56]. Interestingly no clinical disease was reported in these sheep [Citation56]. This supports the hypothesis that such spillover events may be more common than previously recognized.However, comprehensive surveillance for HPAIV is not routinely conducted in the ruminant sector. Should future cases arise whereby suspicion of infection of ruminant species is suspected then it would be critical to have better access to animals for sampling. On this occasion, the fact that sheep were in lamb significantly reduced our ability to sample the herd. Having access to a greater range of sample types, and volumes would allow confirmatory assessments to be made across the herd during the disease event.Certainly, with continued detections of high pathogenicity avian influenza across a broad range of wild and captive mammals globally it is important that a full characterization and assessment of spillover events is undertaken and shared with the global scientific community.
