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

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

  • Nat Commun. 2025 Jul 23;16(1):6771. doi: 10.1038/s41467-025-61757-3.
Thomas P Fabrizio 1,  Ahmed Kandeil 1 2,  Walter N Harrington 1,  Jeremy C Jones 1,  Trushar Jeevan 1,  Konstantin Andreev 1,  Patrick Seiler 1,  Jonathan Fogo 1 3,  Morgan L Davis 1,  Jeri Carol Crumpton 1,  John Franks 1,  Jennifer DeBeauchamp 1,  Peter Vogel 4,  C Scanlon Daniels 5,  Rebecca L Poulson 6,  Andrew S Bowman 7,  Elena A Govorkova 1,  Richard J Webby 8
Affiliations

Affiliations

  • 1 Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • 2 Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza, Egypt.
  • 3 Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA.
  • 4 Department of Comparative Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • 5 Circle H Headquarters LLC, Dalhart, Texas, USA.
  • 6 Southeastern Cooperative Wildlife Disease Study, College of Veterinary Medicine, Department of Population Health, The University of Georgia, Athens, GA, USA.
  • 7 Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
  • 8 Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN, USA. richard.webby@stjude.org.
PMID: 40695800 DOI: 10.1038/s41467-025-61757-3
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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