The emergence and molecular evolution of H5N1 influenza viruses in United States dairy cattle
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.
Authors
- Gytis Dudas (ORCID: https://orcid.org/0000-0002-0227-4158)
- Daniel H. Goldhill (ORCID: https://orcid.org/0000-0003-4597-5963)
- Michael Worobey (ORCID: https://orcid.org/0000-0002-3578-1367)
- Angela L. Rasmussen (ORCID: https://orcid.org/0000-0001-9462-3169)
- Thomas P. Peacock (ORCID: https://orcid.org/0000-0001-7077-2928)
- Florence Débarre (ORCID: https://orcid.org/0000-0003-2497-833X)
- Martha I. Nelson (ORCID: https://orcid.org/0000-0003-4814-0179)
- Marc A. Suchard (ORCID: https://orcid.org/0000-0001-9818-479X)
- Christopher Ruis (ORCID: https://orcid.org/0000-0003-0977-5534)
- Jeffrey B. Joy (ORCID: https://orcid.org/0000-0002-7013-1482)
- L. P. Serrano
- Meera Chand (ORCID: https://orcid.org/0000-0001-7164-352X)
- Oliver G. Pybus (ORCID: https://orcid.org/0000-0002-8797-2667)
- Natalie Groves (ORCID: https://orcid.org/0000-0002-3832-3484)
- Divya Venkatesh
- Joel O. Wertheim (ORCID: https://orcid.org/0000-0003-4882-5856)
- Karthik Gangavarapu
- Alvin Crespo-Bellido (ORCID: https://orcid.org/0000-0002-3462-9072)
- Praneeth Gangavarapu
- Xiang Ji
- Philippe Lemey
- Louise Moncla
- Jonathan E. Pekar
- Moritz U. G. Kraemer
- Kristian G. Andersen
- Andrew Rambaut
Institutions
- Scripps Research Institute (US)
- The Pirbright Institute (GB)
- Centre National de la Recherche Scientifique (FR)
- National Security Agency (US)
- Royal Veterinary College (GB)
- University of Arizona (US)
- University of British Columbia (CA)
- University of California, Los Angeles (US)
- Vilnius University (LT)
- Iowa State University (US)
- Université Paris-Est Créteil (FR)
- Rega Institute for Medical Research (BE)
- University of Cambridge (GB)
- United States National Library of Medicine (US)
- University of Saskatchewan (CA)
- University of California San Diego (US)
- Sorbonne Université (FR)
- University of Oxford (GB)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Lung Institute (US)
- AIDS Vancouver (CA)
- Institut d'écologie et des sciences de l'environnement de Paris (FR)
- Institut de Recherche pour le Développement (FR)
- Imperial College London (GB)
- University of Pennsylvania (US)
- University of Edinburgh (GB)
- KU Leuven (BE)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-01
- DOI
- https://doi.org/10.64898/2026.03.30.713641
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bill and Melinda Gates Foundation
- Rockefeller Foundation
- Wellcome Trust
- UK Research and Innovation
- Fonds Wetenschappelijk Onderzoek
- Novo Nordisk Fonden
- National Institutes of Health