Experimental reproduction of viral replication and disease in dairy calves and lactating cows inoculated with highly pathogenic avian influenza H5N1 clade 2.3.4.4b

Authors: Baker, Amy; Arruda, Bailey; Palmer, Mitchell; Boggiatto, Paola; Sarlo Davila, Kaitlyn; Buckley, Alexandra; ZANELLA, GIOVANA - Oak Ridge Institute For Science And Education (ORISE); SNYDER, CELESTE - Oak Ridge Institute For Science And Education (ORISE); Anderson, Tavis; HUTTER, CARL - Oak Ridge Institute For Science And Education (ORISE); NYUYEN, THAO - Oak Ridge Institute For Science And Education (ORISE); MARKIN, ALEXEY - Iowa State University; LANTZ, KRISTINA - Animal And Plant Health Inspection Service (APHIS); POSEY, ERIN - Animal And Plant Health Inspection Service (APHIS); TORCHETTI, MIA - Animal And Plant Health Inspection Service (APHIS); ROBBE-AUSTERMAN, SUELEE - Animal And Plant Health Inspection Service (APHIS); DREW, MAGSTADT - Iowa State University; PATRICK, GORDEN - Iowa State University

Submitted to: Nature
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/8/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: Highly pathogenic avian influenza (HPAI) H5N1 in the hemagglutinin clade 2.3.4.4b were detected in the United States in late 2021. In addition to impacting poultry, these HPAI viruses caused mortality events in wild bird species and wild mammals. Transmission in multiple host species raises the concern for mammalian adaptation and risk to humans. On March 25, 2024, HPAI H5N1 clade 2.3.4.4b was confirmed in a dairy cow in Texas in response to a multi-state investigation into milk production losses. Over one hundred positive herds were rapidly identified in Texas and eleven other U.S. states. The case description included reduced feed intake and rumen motility in lactating cows, decreased milk production, and thick yellow milk. The diagnostic investigation revealed detections of viral RNA in milk and mammary tissue. To prove the disease was caused by HPAI, we experimentally reproduced infection with genotype B3.13 in Holstein yearling heifers and lactating cows. The heifers were inoculated by an aerosol respiratory route and the cows by an intramammary route. Clinical disease was mild in the 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 consistent with field reports of viral mastitis. Infection was confirmed by high levels of viral RNA detected in milk, virus detection, lesions in mammary tissue, and seroconversion. This study provides the foundation to investigate additional routes of infection, transmission, and intervention strategies like vaccination.

Technical Abstract: Highly pathogenic avian influenza (HPAI) H5N1 of the hemagglutinin clade 2.3.4.4b was detected in the United States in late 2021 and continues to circulate in all four North American flyways to date. In addition to impacting poultry, these HPAI viruses caused mortality events in wild bird species and wild mammals. Transmission in multiple host species raises the concern for mammalian adaptation. On March 25, 2024, HPAI H5N1 clade 2.3.4.4b was confirmed in a dairy cow in Texas in response to a multi-state investigation into milk production losses. Over one hundred positive herds were rapidly identified in Texas and eleven other U.S. states. The case description included reduced feed intake and rumen motility in lactating cows, decreased milk production, and thick yellow milk. The diagnostic investigation revealed detections of viral RNA in milk and mammary tissue with alveolar epithelial degeneration and necrosis, and positive immunoreactivity of glandular epithelium by immunohistochemistry. A single transmission event, likely from avian species to dairy cattle, followed by limited local transmission preceded the onward lateral transmission of H5N1 clade 2.3.4.4b genotype B3.13. We sought to experimentally reproduce infection with genotype B3.13 in Holstein yearling heifers and lactating cows. The heifers were inoculated by an aerosol respiratory route and the cows by an intramammary route. Clinical disease was mild in the 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 consistent with field reports of viral mastitis. 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, transmission, and intervention strategies.