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BioRxiv (preprint) . Detection of clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus in a sheep in Great Britain, 2025

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Editor, Senior Moderator
Detection of clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus in a sheep in Great Britain, 2025

View ORCID ProfileAshley C Banyard, View ORCID ProfileHolly Coombes, Jacob Terrey, Natalie McGinn, James Seekings, Benjamin Clifton, View ORCID ProfileBenjamin Mollett, View ORCID ProfileCecilia Di Genova, Pia Sainz-Dominguez, Laura Worsley, Raquel Jorquera, View ORCID ProfileElizabeth Billington, Edward Fullick, View ORCID ProfileAudra-Lynne Schlachter, View ORCID ProfileDavid Jorge, View ORCID ProfileAlejandro Nunez, Marco Falchieri, View ORCID ProfileJoe James, View ORCID ProfileScott Maclean Reid
doi: https://doi.org/10.1101/2025.06.27.661969 This article is a preprint and has not been certified by peer review [what does this mean?]


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 populations, 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, has 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 undertaken to determine the 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 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 was likely attributable to proximity to infected poultry and a presumed heavily contaminated environment. The implications of this ruminant detection are discussed in the context of interspecies transmission and surveillance strategies.

https://www.biorxiv.org/content/10.1101/2025.06.27.661969v1













 
Excerpts from above report


These laboratory findings, in conjunction with the observed

clinical signs, led to the official confirmation of H5N1 HPAI in avian species on the premises on

18th February 2025 (Figure 1C). Subsequent genetic assessment identified all poultry genomes

as a clade 2.3.4.4b H5N1 HPAIV , belonging to the DI.2 genotype, in accordance with the

established genotype classification system [50].

The viral sequence obtained from the ewe provides the only definitive evidence that

replication occurred within this host as several amino acid substitutions were detected across

multiple genes. 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. Such

changes strongly support 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.

 
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