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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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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