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bioRxiv · 10.1101/2024.08.19.608652

Recent Bovine HPAI H5N1 Isolate is Highly Virulent for Mice, Rapidly Causing Acute Pulmonary and Neurologic Disease

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. U.·Rosenke, K.
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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 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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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. U., Rosenke, K.. 2024-08-19. Recent Bovine HPAI H5N1 Isolate is Highly Virulent for Mice, Rapidly Causing Acute Pulmonary and Neurologic Disease. https://doi.org/10.1101/2024.08.19.608652

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