OmniVira

Literature detail

The emergence and molecular evolution of H5N1 influenza viruses in United States dairy cattle.

Jonathan E Pekar1 Karthik Gangavarapu2 Alvin Crespo-Bellido3 Thomas P Peacock4,5 Joel O Wertheim6 Gytis Dudas7 Jeffrey B Joy8,9,10 Meera Chand11 Florence Débarre12 Praneeth Gangavarapu13 Daniel H Goldhill14 Natalie Groves11 Xiang Ji15 Lorena Malpica Serrano16 Louise Moncla17 Angela L Rasmussen18 Christopher Ruis19,20,21 Divya Venkatesh22 Moritz U G Kraemer22,23 Oliver G Pybus14,22,23 Kristian G Andersen2 Marc A Suchard24 Martha I Nelson3 Philippe Lemey25 Michael Worobey16 Andrew Rambaut1
Affiliations 25 institutions
  1. Institute of Ecology and Evolution, University of Edinburgh, Edinburgh, UK.
  2. Department of Translational Medicine, The Scripps Research Institute, La Jolla, CA, USA.
  3. Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD 20892.
  4. The Pirbright Institute, Woking, UK, GU24 0NF.
  5. Department of Infectious Disease, Imperial College London, UK, W2 1PG.
  6. Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
  7. Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
  8. British Columbia Centre for Excellence in HIV/AIDS.
  9. Bioinformatics, University of British Columbia.
  10. Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
  11. UK Health Security Agency, London UK.
  12. Institut d'Écologie et des Sciences de l'Environnement (IEES-Paris, UMR 7618), CNRS, Sorbonne Université, UPEC, IRD, INRAE, Paris, France.
  13. Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
  14. Department of Pathobiology and Population Sciences, Royal Veterinary College, London, UK.
  15. Department of Statistics, Iowa State University, Ames, IA 50011, USA.
  16. Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85705, USA.
  17. Department of Pathobiology, University of Pennsylvania, PA 19104, USA.
  18. Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada S8N 5E3.
  19. VPD Heart & Lung Research Institute, Department of Medicine, University of Cambridge, Cambridge, UK.
  20. Cambridge Centre for AI in Medicine, University of Cambridge, Cambridge, UK.
  21. Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
  22. Department of Biology, University of Oxford, Oxford OX1 3SY, UK.
  23. Pandemic Sciences Institute, University of Oxford, Oxford, UK.
  24. Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  25. Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium.
PMID 41959054 2026 bioRxiv eng epublish
PubMed DOI Browse context

Article

Publication summary

Prior to 2024, highly pathogenic avian influenza H5N1 clade 2.3.4.4b viruses circulated predominantly in wild birds and poultry. In 2024 and 2025, 2.3.4.4b genotypes B3.13 and D1.1 were detected in United States dairy cattle. Using whole-genome and segment-specific phylodynamic inference, we estimate that B3.13 and D1.1 spilled over from wild birds into dairy cattle in late 2023 and late 2024, respectively. Spillover occurred shortly after the formation of the reassortant genotypes and was followed by months of cryptic transmission prior to detection. We found that both B3.13 and D1.1 evolved at higher rates in cattle relative to birds, primarily due to relaxed purifying selection. Site-specific analyses identified genomic sites under positive selection in cattle relative to birds, indicating adaptation and likely contributing to improved viral fitness after spillover. Intensified genomic surveillance in dairy cattle is essential as population immunity introduces additional selection pressures, with ever-changing risk for human emergence.

Structured evidence records

Evidence records

6 total
Genomic Evolution 2 records
Genomic Evolution Extraction confidence 0.95
Key finding

Whole-genome and phylodynamic analyses showed that H5N1 genotypes B3.13 and D1.1 spilled over from wild birds into dairy cattle in the United States and subsequently evolved more rapidly under relaxed purifying selection and positive selection in cattle.

Virus
IAV H5N1
Host
Bos taurus
Location
Not specified
Supporting text

Using whole-genome and segment-specific phylodynamic inference, we estimate that B3.13 and D1.1 spilled over from wild birds into dairy cattle in late 2023 and late 2024, respectively. ... Site-specific analyses identified genomic sites under positive selection in cattle relative to birds.

Genes or proteins
whole genome
Analysis methods
phylodynamic analysis; whole-genome analysis; site-specific selection analysis
Genomic Evolution Extraction confidence 0.95
Key finding

Whole-genome and phylodynamic analyses showed that H5N1 genotype D1.1 spilled over from wild birds into dairy cattle in the United States and subsequently evolved more rapidly with signatures of positive selection in cattle.

Virus
IAV H5N1
Host
Bos taurus
Location
Not specified
Supporting text

Using whole-genome and segment-specific phylodynamic inference, we estimate that B3.13 and D1.1 spilled over from wild birds into dairy cattle in late 2023 and late 2024, respectively. ... Site-specific analyses identified genomic sites under positive selection in cattle relative to birds.

Genes or proteins
whole genome
Analysis methods
phylodynamic analysis; whole-genome analysis; site-specific selection analysis
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.90
Key finding

H5N1 viruses displayed genomic sites under positive selection in dairy cattle compared with birds, consistent with molecular adaptation that enhanced viral fitness in cattle.

Virus
IAV H5N1
Host
Not specified
Location
Not specified
Supporting text

Site-specific analyses identified genomic sites under positive selection in cattle relative to birds, indicating adaptation and likely contributing to improved viral fitness after spillover.

Mechanism types
molecular_adaptation; positive_selection; replication_efficiency
Recombination Or Reassortment 1 records
Recombination Or Reassortment Extraction confidence 0.85
Key finding

H5N1 clade 2.3.4.4b genotypes B3.13 and D1.1 emerged in United States dairy cattle soon after reassortant genotype formation, suggesting reassortment preceded cross-species transmission.

Virus
IAV H5N1
Host
Not specified
Location
Not specified
Supporting text

Spillover occurred shortly after the formation of the reassortant genotypes and was followed by months of cryptic transmission prior to detection.

Event type
reassortment
Spillover Event 1 records
Spillover Event Extraction confidence 0.95
Key finding

Highly pathogenic avian influenza H5N1 genotypes B3.13 and D1.1 spilled over from wild birds into dairy cattle in the United States in late 2023 and late 2024.

Virus
IAV H5N1
Location
United States United States
Supporting text

Using whole-genome and segment-specific phylodynamic inference, we estimate that B3.13 and D1.1 spilled over from wild birds into dairy cattle in late 2023 and late 2024, respectively.

Method
whole-genome sequencing; segment-specific phylodynamic inference
Study design
phylogenetic analysis
Transmission direction
animal-to-human
Geographic raw
United States
Country inferred
United States
Zoonotic Surveillance 1 records
Zoonotic Surveillance Extraction confidence 0.75
Key finding

Genomic surveillance was conducted in United States dairy cattle for H5N1 influenza viruses to monitor viral evolution and assess zoonotic risk.

Virus
IAV H5N1
Host
Bos taurus
Location
United States United States
Supporting text

Intensified genomic surveillance in dairy cattle is essential as population immunity introduces additional selection pressures, with ever-changing risk for human emergence.

Method
genomic surveillance
Geographic raw
United States
Country inferred
United States