Recent Bovine HPAI H5N1 Isolate 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 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.