Comparative #Distribution of α2,3- and α2,6-Linked Sialic Acid #Receptors and #Influenza #H5N1 Virus #Binding in #Sheep, #Goats, and #Alpacas

 

ABSTRACT

Highly pathogenic avian influenza virus (HPAIV) H5N1 continues to pose a significant threat to animal and human health. Since 2022, an expanded host range has been observed, as illustrated by the H5N1 outbreak in dairy cows. Other minor livestock species, such as sheep, goats, and alpacas, have also tested positive for H5N1 for the first time, raising concerns about its impact on previously overlooked livestock species. In this study, we first characterized the distribution of sialic acid (SA) receptors across respiratory and non-respiratory tissues of sheep, goats, and alpacas using Maackia amurensis (SA α2,3) and Sambucus nigra (SA α2,6) lectins. We found that both SA receptors are present in all tissues across species, with notable differences in their distribution and abundance. Next, we developed recombinant LPAIV H5N1 viruses over a laboratory-adapted backbone to evaluate tissue-specific virus binding profiles. The results show that a representative H5N1 virus from clade 2.3.4.4b binds effectively to respiratory and non-respiratory tissues across all species. The strongest virus binding was observed in sheep, followed by goats and, lastly, alpacas. Similar binding patterns were observed with an LPAIV version of clade 2.3.4.4b and a Gs/Gd lineage precursor prototype virus. Finally, we show that H1N1 and H3N2 viruses also bind to respiratory tissues of sheep and goats. These findings provide important insights into the potential susceptibility of minor livestock species to HPAIV H5N1 and other influenza subtypes. Our results contribute to a better understanding of influenza tissue tropism across livestock species and its potential implications for zoonotic transmission.

IMPORTANCE 

Since 2022, an unprecedented number of Influenza A virus (IAV) H5N1 detections have been reported in mammals. Sheep, goats, and alpacas are often raised in integrated production systems and may serve as hosts at the wildlife-livestock interface. The establishment of H5N1 in any mammalian host also increases its pandemic potential. Our results reveal species- and tissue-dependent patterns of H5N1 attachment and identify tissues that support viral binding. Furthermore, we show that respiratory tissues may be susceptible to other IAV subtypes, suggesting that these species could act as mixing vessels for reassortment events and the emergence of novel IAV strains. These results expand our understanding of the host range and tissue tropism of H5N1 and other IAV subtypes, providing a foundation for targeted surveillance of minor livestock species. Collectively, this work underscores the importance of considering diverse livestock hosts when evaluating the continued spread of H5N1 at the avian-mammalian interface.

Competing Interest Statement

The authors have declared no competing interest.

Source: BioRxIV, https://doi.org/10.64898/2026.10.26.762033

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The identification and genetic characteristics of the #Orf #virus strain (ORFV-CL24) isolated from #Jilin province, #China

 

Abstract

Orf virus (ORFV), the prototype species of the Parapoxvirus genus within the Poxviridae family (subfamily Chordopoxvirinae), is a global pathogen infecting sheep, goats, and other ruminants, with zoonotic potential for humans. In this study, an outbreak of ORFV infection occurred in a sheep flock in Changling County, Jilin province, China, causing papules, pustules, and crusting lesions on the lips and eyelids. Typical parapoxvirus particles were observed using electron microscopy, and a wild ORFV strain was isolated, characterized, and designated as ORFV-CL24. To clarify the epidemiological and genomic characteristics of ORFV in the region, we completed its whole-genome sequencing (GenBank accession number: PV126639). Genome analysis revealed that ORFV-CL24 shares a conserved structure with other isolates available in GenBank, which possess a complete genomic sequence of 138,500 bp of dsDNA harboring 131 putative open reading frames (ORFs) flanked by inverted terminal repeat (ITR) regions of 3,264 bp at both termini. Additionally, the genome exhibited high GC-content (63.3%), indicating its key role in DNA stability. Phylogenetic analysis placed the wild strain within a subclade with the attenuated ORFV strain D1701, implying a putative common ancestor or epidemiological linkages. Further analysis of B2L (ORFV 011) and E3L (ORFV 020) genes further revealed genetic diversity and evolutionary patterns. Notably, despite phylogenetic relatedness, specific mutations in ORF020 further distinguished ORFV-CL24 from D1701, reflecting stepwise mutation accumulation during host adaptation. In conclusion, our results provided valuable genetic insights into ORFV-CL24, which contributed to a better understanding of its evolution, biological properties, and endemic trends in China.

Source: Frontiers in Microbiology, https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2025.1658326/full

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Detection of #antibodies specific to #H5 avian #influenza virus in a #sheep in #Norway, June 2024 ...

 

Abstract

A 2023 outbreak of highly pathogenic avian influenza in seabirds in Norway caused substantial environmental contamination of grazing areas frequented by local sheep. Eleven months later, 220 sheep were tested for antibodies to type A influenza and H5 subtype using ELISA, haemagglutination inhibition, and microneutralisation assays. One ewe (0.5%) tested positive by all methods, consistent with prior spillover infection. This underscores the importance of restricting livestock access to outbreak areas to mitigate cross-species transmission and zoonotic risk.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.08.14.670265v1

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Detection of clade 2.3.4.4b #H5N1 high pathogenicity avian #influenza virus in a #sheep in #UK, 2025

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.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.06.27.661969v1

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#UK, #England: Confirmed findings of #influenza of #avian origin in captive #mammals (as of March 25 '25)

Sheep, March 2025

One domestic sheep (Ovis aries) tested positive for influenza of avian origin (H5N1) in March 2025. The case was identified following routine surveillance of farmed livestock on a premises in Yorkshire where highly pathogenic avian influenza (H5N1) had been confirmed in other captive birds. The single animal was a ewe with signs of mastitis but no other clinical signs. The milk was positive by polymerase chain reaction (PCR) and the blood tested positive for H5 antibodies.  

All affected birds and the infected ewe were humanely culled to mitigate the risk of further disease spread. Further official testing of the remaining flock of sheep were all negative for the presence of avian influenza virus.

Source: DEFRA, https://www.gov.uk/government/publications/bird-flu-avian-influenza-findings-in-captive-mammals/confirmed-findings-of-influenza-of-avian-origin-in-captive-mammals

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