Comparative Distribution of α2,3- and α2,6-Linked Sialic Acid Receptors and Influenza A(H5N1) Virus Binding in Sheep, Goats, and Alpacas
- 1Iowa State University
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 2,3) and Sambucus nigra (SA 2,6) 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.
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BibTeX
@misc{marrero2026comparative,
title = {{Comparative Distribution of α2,3- and α2,6-Linked Sialic Acid Receptors and Influenza A(H5N1) Virus Binding in Sheep, Goats, and Alpacas}},
author = {N. Marrero and E. Blay and S. Oancea and G. Brixius and R. Nelli and P. J. Plummer and J. Groeltz-Thrush and B. Boyle and B. Jones and O. Fasina and T. Harm and C. Siepker and R. Phillips and L. Bradner and A. Hufnagel and M. Zeller and E. Cassmann and S. Carnaccini and T. M. Bell and C. J. Caceres},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.26.762033},
url = {https://www.biorxiv.org/content/10.64898/2026.10.26.762033v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Comparative Distribution of α2,3- and α2,6-Linked Sialic Acid Receptors and Influenza A(H5N1) Virus Binding in Sheep, Goats, and Alpacas
AU - N. Marrero
AU - E. Blay
AU - S. Oancea
AU - G. Brixius
AU - R. Nelli
AU - P. J. Plummer
AU - J. Groeltz-Thrush
AU - B. Boyle
AU - B. Jones
AU - O. Fasina
AU - T. Harm
AU - C. Siepker
AU - R. Phillips
AU - L. Bradner
AU - A. Hufnagel
AU - M. Zeller
AU - E. Cassmann
AU - S. Carnaccini
AU - T. M. Bell
AU - C. J. Caceres
PY - 2026
DA - 2026/10/26
PB - bioRxiv
DO - 10.64898/2026.10.26.762033
UR - https://www.biorxiv.org/content/10.64898/2026.10.26.762033v1
AB - 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 2,3) and Sambucus nigra (SA 2,6) 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.
ER -