Highly pathogenic avian influenza H5N1 clade 2.3.4.4b genotype B3.13 is highly virulent for mice, rapidly causing acute pulmonary and neurologic disease
Abstract 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 compare disease progression and pathology of three recent clade 2.3.4.4...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60407-y |
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| author | Thomas Tipih Vignesh Mariappan Kwe C. Yinda Kimberly Meade-White Matthew Lewis Atsushi Okumura Natalie McCarthy Ekaterina Altynova Shanna S. Leventhal Trenton Bushmaker Chad S. Clancy Emmie de Wit Vincent J. Munster Heinz Feldmann Kyle Rosenke |
| author_facet | Thomas Tipih Vignesh Mariappan Kwe C. Yinda Kimberly Meade-White Matthew Lewis Atsushi Okumura Natalie McCarthy Ekaterina Altynova Shanna S. Leventhal Trenton Bushmaker Chad S. Clancy Emmie de Wit Vincent J. Munster Heinz Feldmann Kyle Rosenke |
| author_sort | Thomas Tipih |
| collection | DOAJ |
| description | Abstract 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 compare disease progression and pathology of three recent clade 2.3.4.4b isolates derived from a cow, a mountain lion, and a mink to a human HPAI A(H5N1) isolate from Vietnam in mice. Inoculating C57BL/6J and BALB/c mice with all four HPAI A(H5N1) isolates results in comparable levels of virus replication in the lung inducing significant local pro-inflammatory cytokine responses and severe respiratory disease. Infecting C57BL/6J mice with the bovine isolate yields high viral titers in the brain, a significant pro-inflammatory cytokine response and neurologic disease. Our findings suggest the recent bovine isolate possesses enhanced neuroinvasive/neurovirulent disease causing fatal respiratory and neurologic disease in C57BL/6J mice. |
| format | Article |
| id | doaj-art-916ddcbb78ae418b82a696db57b7b7e3 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-916ddcbb78ae418b82a696db57b7b7e32025-08-20T03:37:37ZengNature PortfolioNature Communications2041-17232025-07-0116111210.1038/s41467-025-60407-yHighly pathogenic avian influenza H5N1 clade 2.3.4.4b genotype B3.13 is highly virulent for mice, rapidly causing acute pulmonary and neurologic diseaseThomas Tipih0Vignesh Mariappan1Kwe C. Yinda2Kimberly Meade-White3Matthew Lewis4Atsushi Okumura5Natalie McCarthy6Ekaterina Altynova7Shanna S. Leventhal8Trenton Bushmaker9Chad S. Clancy10Emmie de Wit11Vincent J. Munster12Heinz Feldmann13Kyle Rosenke14Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthRocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthAbstract 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 compare disease progression and pathology of three recent clade 2.3.4.4b isolates derived from a cow, a mountain lion, and a mink to a human HPAI A(H5N1) isolate from Vietnam in mice. Inoculating C57BL/6J and BALB/c mice with all four HPAI A(H5N1) isolates results in comparable levels of virus replication in the lung inducing significant local pro-inflammatory cytokine responses and severe respiratory disease. Infecting C57BL/6J mice with the bovine isolate yields high viral titers in the brain, a significant pro-inflammatory cytokine response and neurologic disease. Our findings suggest the recent bovine isolate possesses enhanced neuroinvasive/neurovirulent disease causing fatal respiratory and neurologic disease in C57BL/6J mice.https://doi.org/10.1038/s41467-025-60407-y |
| spellingShingle | Thomas Tipih Vignesh Mariappan Kwe C. Yinda Kimberly Meade-White Matthew Lewis Atsushi Okumura Natalie McCarthy Ekaterina Altynova Shanna S. Leventhal Trenton Bushmaker Chad S. Clancy Emmie de Wit Vincent J. Munster Heinz Feldmann Kyle Rosenke Highly pathogenic avian influenza H5N1 clade 2.3.4.4b genotype B3.13 is highly virulent for mice, rapidly causing acute pulmonary and neurologic disease Nature Communications |
| title | Highly pathogenic avian influenza H5N1 clade 2.3.4.4b genotype B3.13 is highly virulent for mice, rapidly causing acute pulmonary and neurologic disease |
| title_full | Highly pathogenic avian influenza H5N1 clade 2.3.4.4b genotype B3.13 is highly virulent for mice, rapidly causing acute pulmonary and neurologic disease |
| title_fullStr | Highly pathogenic avian influenza H5N1 clade 2.3.4.4b genotype B3.13 is highly virulent for mice, rapidly causing acute pulmonary and neurologic disease |
| title_full_unstemmed | Highly pathogenic avian influenza H5N1 clade 2.3.4.4b genotype B3.13 is highly virulent for mice, rapidly causing acute pulmonary and neurologic disease |
| title_short | Highly pathogenic avian influenza H5N1 clade 2.3.4.4b genotype B3.13 is highly virulent for mice, rapidly causing acute pulmonary and neurologic disease |
| title_sort | highly pathogenic avian influenza h5n1 clade 2 3 4 4b genotype b3 13 is highly virulent for mice rapidly causing acute pulmonary and neurologic disease |
| url | https://doi.org/10.1038/s41467-025-60407-y |
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