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

Thomas Tipih; Vignesh Mariappan; Claude Kwe Yinda; Kimberly D. Meade-White; Matthew C. Lewis; Atsushi Okumura; Natalie McCarthy; Ekaterina S Altynova; Shanna S. Leventhal; Trenton Bushmaker; Chad S. Clancy; Emmie de Wit; Vincent Jacobus Munster; Heinz Feldmann; Kyle Rosenke

doi:10.1038/s41467-025-60407-y

MicrobiologyNature CommunicationsJul 1, 2025

Peer-reviewed journal article

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

Thomas Tipih iD, Vignesh Mariappan iD, Claude Kwe Yinda iD, Kimberly D. Meade-White iD, Matthew C. Lewis iD, Atsushi Okumura iD, Natalie McCarthy, Ekaterina S Altynova iD, Shanna S. Leventhal, Trenton Bushmaker iD, Chad S. Clancy iD, Emmie de Wit iD, Vincent Jacobus Munster iD, Heinz Feldmann iD, Kyle Rosenke iD

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.

PDF DOI