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Recent Bovine HPAI H5N1 Isolate Is Highly Virulent For Mice, Rapidly Causing Acute Pulmonary And Neurologic Disease
Open accessAbstract
The highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b viruses, responsible for the current outbreak in dairy cows in the United States, pose a significant animal and public health threat. In this study, we compared disease progression and pathology of three recent clade 2.3.4.4b isolates derived from a cow, mountain lion, and mink to a human HPAI A(H5N1) isolate from Vietnam in mice. Inoculation of C57BL/6J and BALB/c mice with all four HPAI A(H5N1) isolates resulted in comparable levels of virus replication in the lung inducing severe respiratory disease. C57BL/6J mice infected with the bovine isolate also developed high virus titers in the brain, resulting in a significant pro-inflammatory cytokine response and neurologic disease. Our findings suggest the recent bovine isolate possesses enhanced respiratory and neuroinvasive/neurovirulent properties causing fatal respiratory and neurologic disease in C57BL/6J mice.
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WT C57BL/6J mice are highly susceptible to A/bovine challenge, rapidly developing lethal respiratory and neurological disease.
“We have recently shown that WT C57BL/6J mice are highly susceptible to A/bovine challenge with mice rapidly developing lethal respiratory and neurological disease17.”
From Clade 2.3.4.4b but not historical clade 1 HA replicating RNA vaccine protects against bovine H5N1 challenge in mice (2025) · cites this paper as [17]
C57BL6/J mice challenged with A/bovine develop a severe neurological infection in addition to respiratory infection.
“C57BL6/J mice challenged with A/bovine develop a severe neurological infection in addition to respiratory infection17.”
From Clade 2.3.4.4b but not historical clade 1 HA replicating RNA vaccine protects against bovine H5N1 challenge in mice (2025) · cites this paper as [17]
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Hawman, D. W., Tipih, T., Hodge, E., Stone, E. T., Warner, N., McCarthy, N., Granger, B., Meade-White, K., Leventhal, S., Hatzakis, K., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55546-7 · Cited by 20
Self-citation
Metadata
- Authors
- Tipih, T., Mariappan, V., Yinda, K. C., Meade-White, K., Lewis, M., Okumura, A., McCarthy, N., Clancy, C., de Wit, E., Munster, V. J., Feldmann, H., & Rosenke, K.
- Affiliations
- National Institute of Allergy and Infectious Diseases (US)
- National Institutes of Health (US)
- Corresponding author
- Feldmann, Heinz
- Rosenke, Kyle
- ORCID
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2024-08-19
- OpenAlex
- W4401857303
- Cited by
- 10
- References
- 39
- Citations by year
- 2025: 9 · 2024: 1
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- public-domain
- creativecommons.org/publicdomain/zero/1.0/ (vor)
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, public-domain)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
- Keywords
- highly pathogenic avian influenza, clade 2.3.4.4b, mouse model, neurovirulence, neurological disorders, lung disease, viral replication in brain, inflammatory cytokines, C57BL/6J mice, BALB/c mice
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