Genotype B3.13 influenza A(H5N1) viruses isolated from dairy cattle demonstrate high virulence in laboratory models, but retain avian virus-like properties

Thomas P. Fabrizio, Ahmed Kandeil, Walter N. Harrington, Jeremy C. Jones, Trushar Jeevan, Konstantin Andreev, Patrick Seiler, Jonathan Fogo, Morgan L. Davis, Jeri Carol Crumpton, John Franks, Jennifer DeBeauchamp, Peter Vogel, C. Scanlon Daniels, Rebecca L. Poulson, Andrew S. Bowman, Elena A. Govorkova and Richard J. Webby ()
Additional contact information
Thomas P. Fabrizio: St. Jude Children’s Research Hospital
Ahmed Kandeil: St. Jude Children’s Research Hospital
Walter N. Harrington: St. Jude Children’s Research Hospital
Jeremy C. Jones: St. Jude Children’s Research Hospital
Trushar Jeevan: St. Jude Children’s Research Hospital
Konstantin Andreev: St. Jude Children’s Research Hospital
Patrick Seiler: St. Jude Children’s Research Hospital
Jonathan Fogo: St. Jude Children’s Research Hospital
Morgan L. Davis: St. Jude Children’s Research Hospital
Jeri Carol Crumpton: St. Jude Children’s Research Hospital
John Franks: St. Jude Children’s Research Hospital
Jennifer DeBeauchamp: St. Jude Children’s Research Hospital
Peter Vogel: St. Jude Children’s Research Hospital
C. Scanlon Daniels: Circle H Headquarters LLC
Rebecca L. Poulson: The University of Georgia
Andrew S. Bowman: The Ohio State University
Elena A. Govorkova: St. Jude Children’s Research Hospital
Richard J. Webby: St. Jude Children’s Research Hospital

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract In March 2024, clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses were first detected in U.S. dairy cattle. Similar viruses have since caused 70 zoonotic human infections. To assess changes to zoonotic potential, we characterized A(H5N1) clade 2.3.4.4b viruses isolated from cows’ milk and birds. Bovine-derived viruses are lethal in mice and ferrets and transmit to direct but not airborne contact ferrets. All viruses replicate in human bronchial epithelial cells despite preferentially binding avian virus-like receptors. The bovine-derived viruses remain susceptible to FDA-approved antivirals, and they are inhibited by sera from ferrets vaccinated with WHO-recommended candidate vaccine viruses (CVV) or human sera from clade 2.3.4.4c vaccinees. While 2.3.4.4b viruses induce severe disease in mammalian models, they retain many avian virus-like characteristics. Combined, we conclude that the risk of contemporary bovine-derived viruses to humans not in contact with affected animals is low. However, heightened vigilance remains essential to promptly detect and respond to any changes.

Date: 2025
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DOI: 10.1038/s41467-025-61757-3

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