Dairy cows inoculated with highly pathogenic avian influenza virus H5N1

Amy L. Baker (), Bailey Arruda, Mitchell V. Palmer, Paola Boggiatto, Kaitlyn Sarlo Davila, Alexandra Buckley, Giovana Ciacci Zanella, Celeste A. Snyder, Tavis K. Anderson, Carl R. Hutter, Thao-Quyen Nguyen, Alexey Markin, Kristina Lantz, Erin A. Posey, Mia Kim Torchetti, Suelee Robbe-Austerman, Drew R. Magstadt and Patrick J. Gorden
Additional contact information
Amy L. Baker: United States Department of Agriculture
Bailey Arruda: United States Department of Agriculture
Mitchell V. Palmer: United States Department of Agriculture
Paola Boggiatto: United States Department of Agriculture
Kaitlyn Sarlo Davila: United States Department of Agriculture
Alexandra Buckley: United States Department of Agriculture
Giovana Ciacci Zanella: United States Department of Agriculture
Celeste A. Snyder: United States Department of Agriculture
Tavis K. Anderson: United States Department of Agriculture
Carl R. Hutter: United States Department of Agriculture
Thao-Quyen Nguyen: United States Department of Agriculture
Alexey Markin: United States Department of Agriculture
Kristina Lantz: United States Department of Agriculture
Erin A. Posey: United States Department of Agriculture
Mia Kim Torchetti: United States Department of Agriculture
Suelee Robbe-Austerman: United States Department of Agriculture
Drew R. Magstadt: Iowa State University
Patrick J. Gorden: Iowa State University

Nature, 2025, vol. 637, issue 8047, 913-920

Abstract: Abstract Highly pathogenic avian influenza (HPAI) H5N1 haemagglutinin clade 2.3.4.4b was detected in the USA in 2021. These HPAI viruses caused mortality events in poultry, wild birds and wild mammals. On 25 March 2024, HPAI H5N1 clade 2.3.4.4b was confirmed in a dairy cow in Texas in response to a multistate investigation into milk production losses1. More than 200 positive herds were identified in 14 US states. The case description included reduced feed intake and rumen motility in lactating cows, decreased milk production and thick yellow milk2,3. The diagnostic investigation revealed viral RNA in milk and alveolar epithelial degeneration and necrosis and positive immunoreactivity of glandular epithelium in mammary tissue. A single transmission event, probably from birds, was followed by limited local transmission and onward horizontal transmission of H5N1 clade 2.3.4.4b genotype B3.13 (ref. 4). Here we sought to experimentally reproduce infection with genotype B3.13 in Holstein yearling heifers and lactating cows. Heifers were inoculated by an aerosol respiratory route and cows by an intramammary route. Clinical disease was mild in heifers, but infection was confirmed by virus detection, lesions and seroconversion. Clinical disease in lactating cows included decreased rumen motility, changes to milk appearance and production losses. Infection was confirmed by high levels of viral RNA detected in milk, virus isolation, lesions in mammary tissue and seroconversion. This study provides the foundation to investigate additional routes of infection, pathogenesis, transmission and intervention strategies.

Date: 2025
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DOI: 10.1038/s41586-024-08166-6

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