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

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 co...

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Main Authors: 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, Richard J. Webby
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61757-3
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author 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
Richard J. Webby
author_facet 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
Richard J. Webby
author_sort Thomas P. Fabrizio
collection DOAJ
description 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.
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spelling doaj-art-8d2253904a3942d8bc3cd9bfd750ac942025-08-20T04:02:55ZengNature PortfolioNature Communications2041-17232025-07-0116111210.1038/s41467-025-61757-3Genotype B3.13 influenza A(H5N1) viruses isolated from dairy cattle demonstrate high virulence in laboratory models, but retain avian virus-like propertiesThomas P. Fabrizio0Ahmed Kandeil1Walter N. Harrington2Jeremy C. Jones3Trushar Jeevan4Konstantin Andreev5Patrick Seiler6Jonathan Fogo7Morgan L. Davis8Jeri Carol Crumpton9John Franks10Jennifer DeBeauchamp11Peter Vogel12C. Scanlon Daniels13Rebecca L. Poulson14Andrew S. Bowman15Elena A. Govorkova16Richard J. Webby17Department of Host–Microbe Interactions, St. Jude Children’s Research HospitalDepartment of Host–Microbe Interactions, St. Jude Children’s Research HospitalDepartment of Host–Microbe Interactions, St. Jude Children’s Research HospitalDepartment of Host–Microbe Interactions, St. Jude Children’s Research HospitalDepartment of Host–Microbe Interactions, St. Jude Children’s Research HospitalDepartment of Host–Microbe Interactions, St. Jude Children’s Research HospitalDepartment of Host–Microbe Interactions, St. Jude Children’s Research HospitalDepartment of Host–Microbe Interactions, St. Jude Children’s Research HospitalDepartment of Host–Microbe Interactions, St. Jude Children’s Research HospitalDepartment of Host–Microbe Interactions, St. Jude Children’s Research HospitalDepartment of Host–Microbe Interactions, St. Jude Children’s Research HospitalDepartment of Host–Microbe Interactions, St. Jude Children’s Research HospitalDepartment of Comparative Pathology, St. Jude Children’s Research HospitalCircle H Headquarters LLCSoutheastern Cooperative Wildlife Disease Study, College of Veterinary Medicine, Department of Population Health, The University of GeorgiaDepartment of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State UniversityDepartment of Host–Microbe Interactions, St. Jude Children’s Research HospitalDepartment of Host–Microbe Interactions, St. Jude Children’s Research HospitalAbstract 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.https://doi.org/10.1038/s41467-025-61757-3
spellingShingle 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
Richard J. Webby
Genotype B3.13 influenza A(H5N1) viruses isolated from dairy cattle demonstrate high virulence in laboratory models, but retain avian virus-like properties
Nature Communications
title Genotype B3.13 influenza A(H5N1) viruses isolated from dairy cattle demonstrate high virulence in laboratory models, but retain avian virus-like properties
title_full Genotype B3.13 influenza A(H5N1) viruses isolated from dairy cattle demonstrate high virulence in laboratory models, but retain avian virus-like properties
title_fullStr Genotype B3.13 influenza A(H5N1) viruses isolated from dairy cattle demonstrate high virulence in laboratory models, but retain avian virus-like properties
title_full_unstemmed Genotype B3.13 influenza A(H5N1) viruses isolated from dairy cattle demonstrate high virulence in laboratory models, but retain avian virus-like properties
title_short Genotype B3.13 influenza A(H5N1) viruses isolated from dairy cattle demonstrate high virulence in laboratory models, but retain avian virus-like properties
title_sort genotype b3 13 influenza a h5n1 viruses isolated from dairy cattle demonstrate high virulence in laboratory models but retain avian virus like properties
url https://doi.org/10.1038/s41467-025-61757-3
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